Effects of General Anesthetics on Synaptic Transmission and Plasticity

Jimcy      Platholi; Hugh   C.   Hemmings
doi:10.2174/1570159X19666210803105232
Abstract

General anesthetics depress excitatory and/or enhance inhibitory synaptic transmission principally by modulating the function of glutamatergic or GABAergic synapses, respectively, with relative anesthetic agent-specific mechanisms. Synaptic signaling proteins, including ligand- and voltage-gated ion channels, are targeted by general anesthetics to modulate various synaptic mechanisms, including presynaptic neurotransmitter release, postsynaptic receptor signaling, and dendritic spine dynamics to produce their characteristic acute neurophysiological effects. As synaptic structure and plasticity mediate higher-order functions such as learning and memory, long-term synaptic dysfunction following anesthesia may lead to undesirable neurocognitive consequences depending on the specific anesthetic agent and the vulnerability of the population. Here we review the cellular and molecular mechanisms of transient and persistent general anesthetic alterations of synaptic transmission and plasticity.
Keywords: Anesthesia, synaptic plasticity, presynaptic function, postsynaptic structure, ion channels, synaptic transmission.
« Previous Next »
Graphical Abstract

[1] 
Lukatch, H.S.; MacIver, M.B. Voltage-clamp analysis of halothane effects on GABA(A fast) and GABA(A slow) inhibitory currents. Brain Res.,  1997, 765(1), 108-112.
[http://dx.doi.org/10.1016/S0006-8993(97)00516-7] [PMID: 9310400] 
[2] 
Sonner, J.M.; Zhang, Y.; Stabernack, C.; Abaigar, W.; Xing, Y.; Laster, M.J. GABA(A) receptor blockade antagonizes the immobilizing action of propofol but not ketamine or isoflurane in a dose-related manner. Anesth. Analg.,  2003, 96(3), 706-712.
[PMID: 12598250] 
[3] 
MacIver, M.B. Anesthetic agent-specific effects on synaptic inhibition. Anesth. Analg.,  2014, 119(3), 558-569.
[http://dx.doi.org/10.1213/ANE.0000000000000321] [PMID: 24977633] 
[4] 
Perouansky, M.; Baranov, D.; Salman, M.; Yaari, Y. Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents. A patch-clamp study in adult mouse hippocampal slices. Anesthesiology,  1995, 83(1), 109-119.
[http://dx.doi.org/10.1097/00000542-199507000-00014] [PMID: 7604989] 
[5] 
Maclver, M.B.; Mikulec, A.A.; Amagasu, S.M.; Monroe, F.A. Volatile anesthetics depress glutamate transmission via presynaptic actions. Anesthesiology,  1996, 85(4), 823-834.
[http://dx.doi.org/10.1097/00000542-199610000-00018] [PMID: 8873553] 
[6] 
Jevtović-Todorović, V.; Todorović, S.M.; Mennerick, S.; Powell, S.; Dikranian, K.; Benshoff, N.; Zorumski, C.F.; Olney, J.W. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nat. Med.,  1998, 4(4), 460-463.
[http://dx.doi.org/10.1038/nm0498-460] [PMID: 9546794] 
[7] 
Wakasugi, M.; Hirota, K.; Roth, S.H.; Ito, Y. The effects of general anesthetics on excitatory and inhibitory synaptic transmission in area CA1 of the rat hippocampus in vitro. Anesth. Analg.,  1999, 88(3), 676-680.
[http://dx.doi.org/10.1213/00000539-199903000-00039] [PMID: 10072027] 
[8] 
Pittson, S.; Himmel, A.M.; MacIver, M.B. Multiple synaptic and membrane sites of anesthetic action in the CA1 region of rat hippocampal slices. BMC Neurosci.,  2004, 5, 52.
[http://dx.doi.org/10.1186/1471-2202-5-52] [PMID: 15579203] 
[9] 
Berg-Johnsen, J.; Langmoen, I.A. The effect of isoflurane on unmyelinated and myelinated fibres in the rat brain. Acta Physiol. Scand.,  1986, 127(1), 87-93.
[http://dx.doi.org/10.1111/j.1748-1716.1986.tb07879.x] [PMID: 3728047] 
[10] 
Mikulec, A.A.; Pittson, S.; Amagasu, S.M.; Monroe, F.A.; MacIver, M.B. Halothane depresses action potential conduction in hippocampal axons. Brain Res.,  1998, 796(1-2), 231-238.
[http://dx.doi.org/10.1016/S0006-8993(98)00348-5] [PMID: 9689473] 
[11] 
Wu, X.S.; Sun, J.Y.; Evers, A.S.; Crowder, M.; Wu, L.G. Isoflurane inhibits transmitter release and the presynaptic action potential. Anesthesiology,  2004, 100(3), 663-670.
[http://dx.doi.org/10.1097/00000542-200403000-00029] [PMID: 15108983] 
[12] 
Ouyang, W.; Hemmings, H.C., Jr Depression by isoflurane of the action potential and underlying voltage-gated ion currents in isolated rat neurohypophysial nerve terminals. J. Pharmacol. Exp. Ther.,  2005, 312(2), 801-808.
[http://dx.doi.org/10.1124/jpet.104.074609] [PMID: 15375177] 
[13] 
Baumgart, J.P.; Zhou, Z.Y.; Hara, M.; Cook, D.C.; Hoppa, M.B.; Ryan, T.A.; Hemmings, H.C., Jr Isoflurane inhibits synaptic vesicle exocytosis through reduced Ca2+ influx, not Ca2+-exocytosis coupling. Proc. Natl. Acad. Sci. USA,  2015, 112(38), 11959-11964.
[http://dx.doi.org/10.1073/pnas.1500525112] [PMID: 26351670] 
[14] 
Koyanagi, Y.; Torturo, C.L.; Cook, D.C.; Zhou, Z.; Hemmings, H.C., Jr Role of specific presynaptic calcium channel subtypes in isoflurane inhibition of synaptic vesicle exocytosis in rat hippocampal neurones. Br. J. Anaesth.,  2019, 123(2), 219-227.
[http://dx.doi.org/10.1016/j.bja.2019.03.029] [PMID: 31056238] 
[15] 
Westphalen, R.I.; Hemmings, H.C., Jr Selective depression by general anesthetics of glutamate versus GABA release from isolated cortical nerve terminals. J. Pharmacol. Exp. Ther.,  2003, 304(3), 1188-1196.
[http://dx.doi.org/10.1124/jpet.102.044685] [PMID: 12604696] 
[16] 
Westphalen, R.I.; Hemmings, H.C. Jr Volatile anesthetic effects on glutamate versus GABA release from isolated rat cortical nerve terminals: basal release. J. Pharmacol. Exp. Ther.,  2006, 316(1), 208-215.
[http://dx.doi.org/10.1124/jpet.105.090647] [PMID: 16174801] 
[17] 
Torturo, C.L.; Zhou, Z.Y.; Ryan, T.A.; Hemmings, H.C. Isoflurane
	inhibits dopaminergic synaptic vesicle exocytosis coupled to
	CaV2.1 and CaV2.2 in rat midbrain neurons. eNeuro, 2019, 6(1),
	ENEURO.0278-18.2018., 
[http://dx.doi.org/10.1523/ENEURO.0278-18.2018 ] [PMID: 30680310] 
[18] 
Dickinson, R.; Peterson, B.K.; Banks, P.; Simillis, C.; Martin, J.C.; Valenzuela, C.A.; Maze, M.; Franks, N.P. Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor by the anesthetics xenon and isoflurane: evidence from molecular modeling and electrophysiology. Anesthesiology,  2007, 107(5), 756-767.
[http://dx.doi.org/10.1097/01.anes.0000287061.77674.71] [PMID: 18073551] 
[19] 
Rochefort, N.L.; Konnerth, A. Dendritic spines: from structure to in vivo function. EMBO Rep.,  2012, 13(8), 699-708.
[http://dx.doi.org/10.1038/embor.2012.102] [PMID: 22791026] 
[20] 
Yang, G.; Chang, P.C.; Bekker, A.; Blanck, T.J.; Gan, W.B. Transient effects of anesthetics on dendritic spines and filopodia in the living mouse cortex. Anesthesiology,  2011, 115(4), 718-726.
[http://dx.doi.org/10.1097/ALN.0b013e318229a660] [PMID: 21768874] 
[21] 
Platholi, J.; Herold, K.F.; Hemmings, H.C., Jr; Halpain, S. Isoflurane reversibly destabilizes hippocampal dendritic spines by an actin-dependent mechanism. PLoS One,  2014, 9(7)e102978
[http://dx.doi.org/10.1371/journal.pone.0102978] [PMID: 25068870] 
[22] 
Kirson, E.D.; Yaari, Y.; Perouansky, M. Presynaptic and postsynaptic actions of halothane at glutamatergic synapses in the mouse hippocampus. Br. J. Pharmacol.,  1998, 124(8), 1607-1614.
[http://dx.doi.org/10.1038/sj.bjp.0701996] [PMID: 9756375] 
[23] 
Seeman, P. The membrane expansion theory of anesthesia: direct evidence using ethanol and a high-precision density meter. Experientia,  1974, 30(7), 759-760.
[http://dx.doi.org/10.1007/BF01924170] [PMID: 4847658] 
[24] 
Herold, K.F.; Sanford, R.L.; Lee, W.; Andersen, O.S.; Hemmings, H.C., Jr Clinical concentrations of chemically diverse general anesthetics minimally affect lipid bilayer properties. Proc. Natl. Acad. Sci. USA,  2017, 114(12), 3109-3114.
[http://dx.doi.org/10.1073/pnas.1611717114] [PMID: 28265069] 
[25] 
Tibbs, G.R.; Barrie, A.P.; Van Mieghem, F.J.; McMahon, H.T.; Nicholls, D.G. Repetitive action potentials in isolated nerve terminals in the presence of 4-aminopyridine: effects on cytosolic free Ca2+ and glutamate release. J. Neurochem.,  1989, 53(6), 1693-1699.
[http://dx.doi.org/10.1111/j.1471-4159.1989.tb09232.x] [PMID: 2553862] 
[26] 
Catterall, W.A. Molecular mechanisms of gating and drug block of sodium channels. Novartis Found. Symp.,  2002, 241, 206-218.
[PMID: 11771647] 
[27] 
Lewis, A.H.; Raman, I.M. Resurgent current of voltage-gated Na(+) channels. J. Physiol.,  2014, 592(22), 4825-4838.
[http://dx.doi.org/10.1113/jphysiol.2014.277582] [PMID: 25172941] 
[28] 
Hodgkin, A.L.; Huxley, A.F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol.,  1952, 117(4), 500-544.
[http://dx.doi.org/10.1113/jphysiol.1952.sp004764] [PMID: 12991237] 
[29] 
Ragsdale, D.S.; McPhee, J.C.; Scheuer, T.; Catterall, W.A. Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science,  1994, 265(5179), 1724-1728.
[http://dx.doi.org/10.1126/science.8085162] [PMID: 8085162] 
[30] 
Rehberg, B.; Xiao, Y.H.; Duch, D.S. Central nervous system sodium channels are significantly suppressed at clinical concentrations of volatile anesthetics. Anesthesiology,  1996, 84(5), 1223-1233.
[http://dx.doi.org/10.1097/00000542-199605000-00025] [PMID: 8624017] 
[31] 
OuYang, W.; Hemmings, H.C., Jr Isoform-selective effects of isoflurane on voltage-gated Na+ channels. Anesthesiology,  2007, 107(1), 91-98.
[http://dx.doi.org/10.1097/01.anes.0000268390.28362.4a] [PMID: 17585220] 
[32] 
Herold, K.F.; Hemmings, H.C., Jr Sodium channels as targets for volatile anesthetics. Front. Pharmacol.,  2012, 3, 50.
[http://dx.doi.org/10.3389/fphar.2012.00050] [PMID: 22479247] 
[33] 
Ratnakumari, L.; Hemmings, H.C., Jr Inhibition of presynaptic sodium channels by halothane. Anesthesiology,  1998, 88(4), 1043-1054.
[http://dx.doi.org/10.1097/00000542-199804000-00025] [PMID: 9579514] 
[34] 
Ouyang, W.; Wang, G.; Hemmings, H.C., Jr Isoflurane and propofol inhibit voltage-gated sodium channels in isolated rat neurohypophysial nerve terminals. Mol. Pharmacol.,  2003, 64(2), 373-381.
[http://dx.doi.org/10.1124/mol.64.2.373] [PMID: 12869642] 
[35] 
Palti, Y.; Adelman, W.J., Jr Measurement of axonal membrane conductances and capacity by means of a varying potential control voltage clamp. J. Membr. Biol.,  1969, 1(1), 431-458.
[http://dx.doi.org/10.1007/BF01869791] [PMID: 24174059] 
[36] 
Rudy, B. Slow inactivation of the sodium conductance in squid giant axons. Pronase resistance. J. Physiol.,  1978, 283, 1-21.
[http://dx.doi.org/10.1113/jphysiol.1978.sp012485] [PMID: 722569] 
[37] 
Stafstrom, C.E. Persistent sodium current and its role in epilepsy. Epilepsy Curr.,  2007, 7(1), 15-22.
[http://dx.doi.org/10.1111/j.1535-7511.2007.00156.x] [PMID: 17304346] 
[38] 
Zhao, W.; Zhang, M.; Liu, J.; Liang, P.; Wang, R.; Hemmings, H.C.; Zhou, C. Isoflurane modulates hippocampal cornu ammonis pyramidal neuron excitability by inhibition of both transient and persistent sodium currents in mice. Anesthesiology,  2019, 131(1), 94-104.
[http://dx.doi.org/10.1097/ALN.0000000000002753] [PMID: 31166240] 
[39] 
Ratnakumari, L.; Hemmings, H.C., Jr Effects of propofol on sodium channel-dependent sodium influx and glutamate release in rat cerebrocortical synaptosomes. Anesthesiology,  1997, 86(2), 428-439.
[http://dx.doi.org/10.1097/00000542-199702000-00018] [PMID: 9054261] 
[40] 
Liu, Q.Z.; Hao, M.; Zhou, Z.Y.; Ge, J.L.; Wu, Y.C.; Zhao, L.L.; Wu, X.; Feng, Y.; Gao, H.; Li, S.; Xue, L. Propofol reduces synaptic strength by inhibiting sodium and calcium channels at nerve terminals. Protein Cell,  2019, 10(9), 688-693.
[http://dx.doi.org/10.1007/s13238-019-0624-1] [PMID: 31028590] 
[41] 
Ratnakumari, L.; Hemmings, H.C. Jr Inhibition by propofol of [3H]-batrachotoxinin-A 20-alpha-benzoate binding to voltage-dependent sodium channels in rat cortical synaptosomes. Br. J. Pharmacol.,  1996, 119(7), 1498-1504.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb16064.x] [PMID: 8968561] 
[42] 
Reckziegel, G.; Friederich, P.; Urban, B.W. Ketamine effects on human neuronal Na+ channels. Eur. J. Anaesthesiol.,  2002, 19(9), 634-640.
[http://dx.doi.org/10.1017/S0265021502001047] [PMID: 12243285] 
[43] 
Frenkel, C.; Urban, B.W. Molecular actions of racemic ketamine on human CNS sodium channels. Br. J. Anaesth.,  1992, 69(3), 292-297.
[http://dx.doi.org/10.1093/bja/69.3.292] [PMID: 1327042] 
[44] 
Catterall, W.A. From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron,  2000, 26(1), 13-25.
[http://dx.doi.org/10.1016/S0896-6273(00)81133-2] [PMID: 10798388] 
[45] 
Goldin, A.L. Resurgence of sodium channel research. Annu. Rev. Physiol.,  2001, 63, 871-894.
[http://dx.doi.org/10.1146/annurev.physiol.63.1.871] [PMID: 11181979] 
[46] 
Black, J.A.; Waxman, S.G. Sodium channel expression: a dynamic process in neurons and non-neuronal cells. Dev. Neurosci.,  1996, 18(3), 139-152.
[http://dx.doi.org/10.1159/000111403] [PMID: 8894443] 
[47] 
Wood, J.N.; Baker, M. Voltage-gated sodium channels. Curr. Opin. Pharmacol.,  2001, 1(1), 17-21.
[http://dx.doi.org/10.1016/S1471-4892(01)00007-8] [PMID: 11712529] 
[48] 
Purtell, K.; Gingrich, K.J.; Ouyang, W.; Herold, K.F.; Hemmings, H.C., Jr Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane. Br. J. Anaesth.,  2015, 115(1), 112-121.
[http://dx.doi.org/10.1093/bja/aev203] [PMID: 26089447] 
[49] 
Zhou, C.; Johnson, K.W.; Herold, K.F.; Hemmings, H.C., Jr Differential inhibition of neuronal sodium channel subtypes by the general anesthetic isoflurane. J. Pharmacol. Exp. Ther.,  2019, 369(2), 200-211.
[http://dx.doi.org/10.1124/jpet.118.254938] [PMID: 30792243] 
[50] 
Shiraishi, M.; Harris, R.A. Effects of alcohols and anesthetics on recombinant voltage-gated Na+ channels. J. Pharmacol. Exp. Ther.,  2004, 309(3), 987-994.
[http://dx.doi.org/10.1124/jpet.103.064063] [PMID: 14978193] 
[51] 
Rehberg, B.; Duch, D.S. Suppression of central nervous system sodium channels by propofol. Anesthesiology,  1999, 91(2), 512-520.
[http://dx.doi.org/10.1097/00000542-199908000-00026] [PMID: 10443615] 
[52] 
Lai, H.C.; Jan, L.Y. The distribution and targeting of neuronal voltage-gated ion channels. Nat. Rev. Neurosci.,  2006, 7(7), 548-562.
[http://dx.doi.org/10.1038/nrn1938] [PMID: 16791144] 
[53] 
Ogiwara, I.; Miyamoto, H.; Morita, N.; Atapour, N.; Mazaki, E.; Inoue, I.; Takeuchi, T.; Itohara, S.; Yanagawa, Y.; Obata, K.; Furuichi, T.; Hensch, T.K.; Yamakawa, K. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J. Neurosci.,  2007, 27(22), 5903-5914.
[http://dx.doi.org/10.1523/JNEUROSCI.5270-06.2007] [PMID: 17537961] 
[54] 
Lorincz, A.; Nusser, Z. Cell-type-dependent molecular composition of the axon initial segment. J. Neurosci.,  2008, 28(53), 14329-14340.
[http://dx.doi.org/10.1523/JNEUROSCI.4833-08.2008] [PMID: 19118165] 
[55] 
Johnson, K.W.; Herold, K.F.; Milner, T.A.; Hemmings, H.C., Jr; Platholi, J. Sodium channel subtypes are differentially localized to pre- and post-synaptic sites in rat hippocampus. J. Comp. Neurol.,  2017, 525(16), 3563-3578.
[http://dx.doi.org/10.1002/cne.24291] [PMID: 28758202] 
[56] 
Hodgson, P.S.; Liu, S.S.; Gras, T.W. Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo-controlled trial. Anesthesiology,  1999, 91(6), 1687-1692.
[http://dx.doi.org/10.1097/00000542-199912000-00021] [PMID: 10598611] 
[57] 
De Santi, L.; Polimeni, G.; Cuzzocrea, S.; Esposito, E.; Sessa, E.;
Annunziata, P.; Bramanti, P. Neuroinflammation and neuroprotection:
an update on (future) neurotrophin-related strategies in multiple
sclerosis treatment. Curr. Med. Chem.,. 2011, 18(12), 1775-1784.
[http://dx.doi.org/10.2174/092986711795496881] [PMID: 21466473] 
[58] 
Zhang, Y.; Laster, M.J.; Eger, E.I., II; Sharma, M.; Sonner, J.M. Lidocaine, MK-801, and MAC. Anesth. Analg.,  2007, 104(5), 1098-1102.
[http://dx.doi.org/10.1213/01.ane.0000260318.60504.a9] [PMID: 17456658] 
[59] 
Zhang, Y.; Guzinski, M.; Eger, E.I., II; Laster, M.J.; Sharma, M.; Harris, R.A.; Hemmings, H.C., Jr Bidirectional modulation of isoflurane potency by intrathecal tetrodotoxin and veratridine in rats. Br. J. Pharmacol.,  2010, 159(4), 872-878.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00583.x] [PMID: 20105175] 
[60] 
Laster, M.J.; Zhang, Y.; Eger, E.I., II; Shnayderman, D.; Sonner, J.M. Alterations in spinal, but not cerebral, cerebrospinal fluid Na+ concentrations affect the isoflurane minimum alveolar concentration in rats. Anesth. Analg.,  2007, 105(3), 661-665.
[http://dx.doi.org/10.1213/01.ane.0000278090.88402.26] [PMID: 17717220] 
[61] 
Zhang, Y.; Sharma, M.; Eger, E.I., II; Laster, M.J.; Hemmings, H.C., Jr; Harris, R.A. Intrathecal veratridine administration increases minimum alveolar concentration in rats. Anesth. Analg.,  2008, 107(3), 875-878.
[http://dx.doi.org/10.1213/ane.0b013e3181815fbc] [PMID: 18713899] 
[62] 
Pal, D.; Jones, J.M.; Wisidagamage, S.; Meisler, M.H.; Mashour, G.A. Reduced Nav1.6 sodium channel activity in mice increases In Vivo sensitivity to volatile anesthetics. PLoS One,  2015, 10(8)e0134960
[http://dx.doi.org/10.1371/journal.pone.0134960] [PMID: 26252017] 
[63] 
Arhem, P.; Klement, G.; Nilsson, J. Mechanisms of anesthesia: towards integrating network, cellular, and molecular level modeling. Neuropsychopharmacology,  2003, 28(Suppl. 1), S40-S47.
[http://dx.doi.org/10.1038/sj.npp.1300142] [PMID: 12827143] 
[64] 
Hentschke, H.; Raz, A.; Krause, B.M.; Murphy, C.A.; Banks, M.I. Disruption of cortical network activity by the general anaesthetic isoflurane. Br. J. Anaesth.,  2017, 119(4), 685-696.
[http://dx.doi.org/10.1093/bja/aex199] [PMID: 29121295] 
[65] 
Cantrell, A.R.; Catterall, W.A. Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat. Rev. Neurosci.,  2001, 2(6), 397-407.
[http://dx.doi.org/10.1038/35077553] [PMID: 11389473] 
[66] 
Carr, D.B.; Day, M.; Cantrell, A.R.; Held, J.; Scheuer, T.; Catterall, W.A.; Surmeier, D.J. Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity. Neuron,  2003, 39(5), 793-806.
[http://dx.doi.org/10.1016/S0896-6273(03)00531-2] [PMID: 12948446] 
[67] 
Yin, L.; Rasch, M.J.; He, Q.; Wu, S.; Dou, F.; Shu, Y. selective modulation of axonal sodium channel subtypes by 5-HT1A receptor in cortical pyramidal neuron. Cereb. Cortex,  2017, 27(1), 509-521.
[PMID: 26494800] 
[68] 
Maurice, N.; Tkatch, T.; Meisler, M.; Sprunger, L.K.; Surmeier, D.J. D1/D5 dopamine receptor activation differentially modulates rapidly inactivating and persistent sodium currents in prefrontal cortex pyramidal neurons. J. Neurosci.,  2001, 21(7), 2268-2277.
[http://dx.doi.org/10.1523/JNEUROSCI.21-07-02268.2001] [PMID: 11264302] 
[69] 
Chen, Y.; Yu, F.H.; Sharp, E.M.; Beacham, D.; Scheuer, T.; Catterall, W.A. Functional properties and differential neuromodulation of Na(v)1.6 channels. Mol. Cell. Neurosci.,  2008, 38(4), 607-615.
[http://dx.doi.org/10.1016/j.mcn.2008.05.009] [PMID: 18599309] 
[70] 
Hemmings, H.C., Jr; Adamo, A.I. Effects of halothane and propofol on purified brain protein kinase C activation. Anesthesiology,  1994, 81(1), 147-155.
[http://dx.doi.org/10.1097/00000542-199407000-00021] [PMID: 8042784] 
[71] 
Hemmings, H.C., Jr; Adamo, A.I. Activation of endogenous protein kinase C by halothane in synaptosomes. Anesthesiology,  1996, 84(3), 652-662.
[http://dx.doi.org/10.1097/00000542-199603000-00021] [PMID: 8659794] 
[72] 
Jahn, R.; Fasshauer, D. Molecular machines governing exocytosis of synaptic vesicles. Nature,  2012, 490(7419), 201-207.
[http://dx.doi.org/10.1038/nature11320] [PMID: 23060190] 
[73] 
Südhof, T.C. The molecular machinery of neurotransmitter release (Nobel lecture). Angew. Chem. Int. Ed. Engl.,  2014, 53(47), 12696-12717.
[http://dx.doi.org/10.1002/anie.201406359] [PMID: 25339369] 
[74] 
Catterall, W.A. Voltage-gated calcium channels. Cold Spring Harb. Perspect. Biol.,  2011, 3(8)a003947
[http://dx.doi.org/10.1101/cshperspect.a003947] [PMID: 21746798] 
[75] 
Simms, B.A.; Zamponi, G.W. Neuronal voltage-gated calcium channels: structure, function, and dysfunction. Neuron,  2014, 82(1), 24-45.
[http://dx.doi.org/10.1016/j.neuron.2014.03.016] [PMID: 24698266] 
[76] 
Miao, N.; Frazer, M.J.; Lynch, C., III Volatile anesthetics depress Ca2+ transients and glutamate release in isolated cerebral synaptosomes. Anesthesiology,  1995, 83(3), 593-603.
[http://dx.doi.org/10.1097/00000542-199509000-00019] [PMID: 7661360] 
[77] 
Hemmings, H.C., Jr; Yan, W.; Westphalen, R.I.; Ryan, T.A. The general anesthetic isoflurane depresses synaptic vesicle exocytosis. Mol. Pharmacol.,  2005, 67(5), 1591-1599.
[http://dx.doi.org/10.1124/mol.104.003210] [PMID: 15728262] 
[78] 
Daniell, L.C.; Harris, R.A. Neuronal intracellular calcium concentrations are altered by anesthetics: relationship to membrane fluidization. J. Pharmacol. Exp. Ther.,  1988, 245(1), 1-7.
[PMID: 3361437] 
[79] 
Mody, I.; Tanelian, D.L.; MacIver, M.B. Halothane enhances tonic neuronal inhibition by elevating intracellular calcium. Brain Res.,  1991, 538(2), 319-323.
[http://dx.doi.org/10.1016/0006-8993(91)90447-4] [PMID: 1901506] 
[80] 
Nicoll, R.A.; Madison, D.V. General anesthetics hyperpolarize neurons in the vertebrate central nervous system. Science,  1982, 217(4564), 1055-1057.
[http://dx.doi.org/10.1126/science.7112112] [PMID: 7112112] 
[81] 
Kitamura, A.; Marszalec, W.; Yeh, J.Z.; Narahashi, T. Effects of halothane and propofol on excitatory and inhibitory synaptic transmission in rat cortical neurons. J. Pharmacol. Exp. Ther.,  2003, 304(1), 162-171.
[http://dx.doi.org/10.1124/jpet.102.043273] [PMID: 12490587] 
[82] 
Krnjević, K.; Puil, E. Halothane suppresses slow inward currents in hippocampal slices. Can. J. Physiol. Pharmacol.,  1988, 66(12), 1570-1575.
[http://dx.doi.org/10.1139/y88-257] [PMID: 3228790] 
[83] 
el-Beheiry, H.; Puil, E. Anaesthetic depression of excitatory synaptic transmission in neocortex. Exp. Brain Res.,  1989, 77(1), 87-93.
[http://dx.doi.org/10.1007/BF00250570] [PMID: 2551715] 
[84] 
Bleakman, D.; Jones, M.V.; Harrison, N.L. The effects of four general anesthetics on intracellular [Ca2+] in cultured rat hippocampal neurons. Neuropharmacology,  1995, 34(5), 541-551.
[http://dx.doi.org/10.1016/0028-3908(95)00022-X] [PMID: 7566489] 
[85] 
Wamil, A.W.; Franks, J.J.; Janicki, P.K.; Horn, J.L.; Franks, W.T. Halothane alters electrical activity and calcium dynamics in cultured mouse cortical, spinal cord, and dorsal root ganglion neurons. Neurosci. Lett.,  1996, 216(2), 93-96.
[http://dx.doi.org/10.1016/0304-3940(96)13003-2] [PMID: 8904791] 
[86] 
Olivera, B.M.; Miljanich, G.P.; Ramachandran, J.; Adams, M.E. Calcium channel diversity and neurotransmitter release: the omega-conotoxins and omega-agatoxins. Annu. Rev. Biochem.,  1994, 63, 823-867.
[http://dx.doi.org/10.1146/annurev.bi.63.070194.004135] [PMID: 7979255] 
[87] 
Catterall, W.A. Structure and function of neuronal Ca2+ channels and their role in neurotransmitter release. Cell Calcium,  1998, 24(5-6), 307-323.
[http://dx.doi.org/10.1016/S0143-4160(98)90055-0] [PMID: 10091001] 
[88] 
Wheeler, D.B.; Sather, W.A.; Randall, A.; Tsien, R.W. Distinctive properties of a neuronal calcium channel and its contribution to excitatory synaptic transmission in the central nervous system. Adv. Second Messenger Phosphoprotein Res.,  1994, 29, 155-171.
[http://dx.doi.org/10.1016/S1040-7952(06)80014-5] [PMID: 7848709] 
[89] 
Study, R.E. Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons. Anesthesiology,  1994, 81(1), 104-116.
[http://dx.doi.org/10.1097/00000542-199407000-00016] [PMID: 8042778] 
[90] 
Xu, F.; Sarti, P.; Zhang, J.; Blanck, T.J. Halothane and isoflurane alter calcium dynamics in rat cerebrocortical synaptosomes. Anesth. Analg.,  1998, 87(3), 701-710.
[PMID: 9728857] 
[91] 
Hall, A.C.; Lieb, W.R.; Franks, N.P. Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics. Anesthesiology,  1994, 81(1), 117-123.
[http://dx.doi.org/10.1097/00000542-199407000-00017] [PMID: 8042779] 
[92] 
Mintz, I.M.; Venema, V.J.; Swiderek, K.M.; Lee, T.D.; Bean, B.P.; Adams, M.E. P-type calcium channels blocked by the spider toxin omega-Aga-IVA. Nature,  1992, 355(6363), 827-829.
[http://dx.doi.org/10.1038/355827a0] [PMID: 1311418] 
[93] 
Uchitel, O.D.; Protti, D.A.; Sanchez, V.; Cherksey, B.D.; Sugimori, M.; Llinás, R. P-type voltage-dependent calcium channel mediates presynaptic calcium influx and transmitter release in mammalian synapses. Proc. Natl. Acad. Sci. USA,  1992, 89(8), 3330-3333.
[http://dx.doi.org/10.1073/pnas.89.8.3330] [PMID: 1348859] 
[94] 
Kamatchi, G.L.; Chan, C.K.; Snutch, T.; Durieux, M.E.; Lynch, C. III Volatile anesthetic inhibition of neuronal Ca channel currents expressed in Xenopus oocytes. Brain Res.,  1999, 831(1-2), 85-96.
[http://dx.doi.org/10.1016/S0006-8993(99)01401-8] [PMID: 10411986] 
[95] 
Rajagopal, S.; Fang, H.; Lynch, C., III; Sando, J.J.; Kamatchi, G.L. Effects of isoflurane on the expressed Cav2.2 currents in Xenopus oocytes depend on the activation of protein kinase Cδ and its phosphorylation sites in the Cav2.2α1 subunits. Neuroscience,  2011, 182, 232-240.
[http://dx.doi.org/10.1016/j.neuroscience.2011.02.041] [PMID: 21402126] 
[96] 
Takei, T.; Saegusa, H.; Zong, S.; Murakoshi, T.; Makita, K.; Tanabe, T. Anesthetic sensitivities to propofol and halothane in mice lacking the R-type (Cav2.3) Ca2+ channel. Anesth. Analg.,  2003, 97(1), 96-103.
[http://dx.doi.org/10.1213/01.ANE.0000065548.83253.5C] [PMID: 12818950] 
[97] 
Wu, L.G.; Borst, J.G.; Sakmann, B. R-type Ca2+ currents evoke transmitter release at a rat central synapse. Proc. Natl. Acad. Sci. USA,  1998, 95(8), 4720-4725.
[http://dx.doi.org/10.1073/pnas.95.8.4720] [PMID: 9539805] 
[98] 
Ashby, M.C.; Tepikin, A.V. ER calcium and the functions of intracellular organelles. Semin. Cell Dev. Biol.,  2001, 12(1), 11-17.
[http://dx.doi.org/10.1006/scdb.2000.0212] [PMID: 11162742] 
[99] 
Wei, H.; Liang, G.; Yang, H.; Wang, Q.; Hawkins, B.; Madesh, M.; Wang, S.; Eckenhoff, R.G. The common inhalational anesthetic isoflurane induces apoptosis via activation of inositol 1,4,5-trisphosphate receptors. Anesthesiology,  2008, 108(2), 251-260.
[http://dx.doi.org/10.1097/01.anes.0000299435.59242.0e] [PMID: 18212570] 
[100] 
Murayama, T.; Ogawa, Y. Properties of Ryr3 ryanodine receptor isoform in mammalian brain. J. Biol. Chem.,  1996, 271(9), 5079-5084.
[http://dx.doi.org/10.1074/jbc.271.9.5079] [PMID: 8617786] 
[101] 
Verkhratsky, A. Physiology and pathophysiology of the calcium store in the endoplasmic reticulum of neurons. Physiol. Rev.,  2005, 85(1), 201-279.
[http://dx.doi.org/10.1152/physrev.00004.2004] [PMID: 15618481] 
[102] 
Liu, X.; Betzenhauser, M.J.; Reiken, S.; Meli, A.C.; Xie, W.; Chen, B.X.; Arancio, O.; Marks, A.R. Role of leaky neuronal ryanodine receptors in stress-induced cognitive dysfunction. Cell,  2012, 150(5), 1055-1067.
[http://dx.doi.org/10.1016/j.cell.2012.06.052] [PMID: 22939628] 
[103] 
de Juan-Sanz, J.; Holt, G.T.; Schreiter, E.R.; de Juan, F.; Kim, D.S.; Ryan, T.A. Axonal endoplasmic reticulum Ca2+ content controls release probability in CNS nerve terminals. Neuron,  2017, 93(4), 867-881.e6.
[http://dx.doi.org/10.1016/j.neuron.2017.01.010] [PMID: 28162809] 
[104] 
Gomez, R.S.; Guatimosim, C.; Barbosa, J., Jr; Massensini, A.R.; Gomez, M.V.; Prado, M.A. Halothane-induced intracellular calcium release in cholinergic cells. Brain Res.,  2001, 921(1-2), 106-114.
[http://dx.doi.org/10.1016/S0006-8993(01)03098-0] [PMID: 11720716] 
[105] 
Pinheiro, A.C.; Gomez, R.S.; Guatimosim, C.; Silva, J.H.; Prado, M.A.; Gomez, M.V. The effect of sevoflurane on intracellular calcium concentration from cholinergic cells. Brain Res. Bull.,  2006, 69(2), 147-152.
[http://dx.doi.org/10.1016/j.brainresbull.2005.11.016] [PMID: 16533663] 
[106] 
Jiang, D.; Chen, W.; Xiao, J.; Wang, R.; Kong, H.; Jones, P.P.; Zhang, L.; Fruen, B.; Chen, S.R. Reduced threshold for luminal Ca2+ activation of RyR1 underlies a causal mechanism of porcine malignant hyperthermia. J. Biol. Chem.,  2008, 283(30), 20813-20820.
[http://dx.doi.org/10.1074/jbc.M801944200] [PMID: 18505726] 
[107] 
Rosenberg, H.; Pollock, N.; Schiemann, A.; Bulger, T.; Stowell, K. Malignant hyperthermia: a review. Orphanet J. Rare Dis.,  2015, 10, 93.
[http://dx.doi.org/10.1186/s13023-015-0310-1] [PMID: 26238698] 
[108] 
Kim, S.H.; Ryan, T.A. Balance of calcineurin Aα and CDK5 activities sets release probability at nerve terminals. J. Neurosci.,  2013, 33(21), 8937-8950.
[http://dx.doi.org/10.1523/JNEUROSCI.4288-12.2013] [PMID: 23699505] 
[109] 
Pocock, G.; Richards, C.D. Hydrogen ion regulation in rat cerebellar granule cells studied by single-cell fluorescence microscopy. Eur. J. Neurosci.,  1992, 4(2), 136-143.
[http://dx.doi.org/10.1111/j.1460-9568.1992.tb00860.x] [PMID: 12106376] 
[110] 
Schlame, M.; Hemmings, H.C., Jr Inhibition by volatile anesthetics of endogenous glutamate release from synaptosomes by a presynaptic mechanism. Anesthesiology,  1995, 82(6), 1406-1416.
[http://dx.doi.org/10.1097/00000542-199506000-00012] [PMID: 7793654] 
[111] 
Wang, H.Y.; Eguchi, K.; Yamashita, T.; Takahashi, T. Frequency-dependent block of excitatory neurotransmission by isoflurane via dual presynaptic mechanisms. J. Neurosci.,  2020, 40(21), 4103-4115.
[http://dx.doi.org/10.1523/JNEUROSCI.2946-19.2020] [PMID: 32327530] 
[112] 
Lingamaneni, R.; Birch, M.L.; Hemmings, H.C., Jr Widespread inhibition of sodium channel-dependent glutamate release from isolated nerve terminals by isoflurane and propofol. Anesthesiology,  2001, 95(6), 1460-1466.
[http://dx.doi.org/10.1097/00000542-200112000-00027] [PMID: 11748406] 
[113] 
Westphalen, R.I.; Kwak, N.B.; Daniels, K.; Hemmings, H.C., Jr Regional differences in the effects of isoflurane on neurotransmitter release. Neuropharmacology,  2011, 61(4), 699-706.
[http://dx.doi.org/10.1016/j.neuropharm.2011.05.013] [PMID: 21651920] 
[114] 
Vanini, G.; Watson, C.J.; Lydic, R.; Baghdoyan, H.A. Gamma-aminobutyric acid-mediated neurotransmission in the pontine reticular formation modulates hypnosis, immobility, and breathing during isoflurane anesthesia. Anesthesiology,  2008, 109(6), 978-988.
[http://dx.doi.org/10.1097/ALN.0b013e31818e3b1b] [PMID: 19034094] 
[115] 
Murugaiah, K.D.; Hemmings, H.C., Jr Effects of intravenous general anesthetics on [3H]GABA release from rat cortical synaptosomes. Anesthesiology,  1998, 89(4), 919-928.
[http://dx.doi.org/10.1097/00000542-199810000-00017] [PMID: 9778010] 
[116] 
Bieda, M.C.; MacIver, M.B. Major role for tonic GABAA conductances in anesthetic suppression of intrinsic neuronal excitability. J. Neurophysiol.,  2004, 92(3), 1658-1667.
[http://dx.doi.org/10.1152/jn.00223.2004] [PMID: 15140905] 
[117] 
Augustine, G.J. How does calcium trigger neurotransmitter release? Curr. Opin. Neurobiol.,  2001, 11(3), 320-326.
[http://dx.doi.org/10.1016/S0959-4388(00)00214-2] [PMID: 11399430] 
[118] 
Chapman, E.R. How does synaptotagmin trigger neurotransmitter release? Annu. Rev. Biochem.,  2008, 77, 615-641.
[http://dx.doi.org/10.1146/annurev.biochem.77.062005.101135] [PMID: 18275379] 
[119] 
Paul, A.; Crow, M.; Raudales, R.; He, M.; Gillis, J.; Huang, Z.J. Transcriptional Architecture of synaptic communication delineates GABAergic neuron identity. Cell,  2017, 171(3), 522-539.e20.
[http://dx.doi.org/10.1016/j.cell.2017.08.032] [PMID: 28942923] 
[120] 
Hemmings, H.C. Molecular Targets of General Anesthetics in the Nervous System.Suppressing the Mind: Anesthetic Modulation of Memory and Consciousness; Hudetz, A.; Pearce, R., Eds.; Humana Press: Totowa, NJ, 2010, pp. 11-31.
[121] 
Hu, H.; Jonas, P. A supercritical density of Na(+) channels ensures fast signaling in GABAergic interneuron axons. Nat. Neurosci.,  2014, 17(5), 686-693.
[http://dx.doi.org/10.1038/nn.3678] [PMID: 24657965] 
[122] 
Li, T.; Tian, C.; Scalmani, P.; Frassoni, C.; Mantegazza, M.; Wang, Y.; Yang, M.; Wu, S.; Shu, Y. Action potential initiation in neocortical inhibitory interneurons. PLoS Biol.,  2014, 12(9)e1001944
[http://dx.doi.org/10.1371/journal.pbio.1001944] [PMID: 25203314] 
[123] 
Westphalen, R.I.; Yu, J.; Krivitski, M.; Jih, T.Y.; Hemmings, H.C., Jr Regional differences in nerve terminal Na+ channel subtype expression and Na+ channel-dependent glutamate and GABA release in rat CNS. J. Neurochem.,  2010, 113(6), 1611-1620.
[http://dx.doi.org/10.1111/j.1471-4159.2010.06722.x] [PMID: 20374421] 
[124] 
Buggy, D.J.; Nicol, B.; Rowbotham, D.J.; Lambert, D.G. Effects of intravenous anesthetic agents on glutamate release: a role for GABAA receptor-mediated inhibition. Anesthesiology,  2000, 92(4), 1067-1073.
[http://dx.doi.org/10.1097/00000542-200004000-00025] [PMID: 10754627] 
[125] 
Thureson-Klein, A. Exocytosis from large and small dense cored vesicles in noradrenergic nerve terminals. Neuroscience,  1983, 10(2), 245-259.
[http://dx.doi.org/10.1016/0306-4522(83)90132-X] [PMID: 6633860] 
[126] 
Rizo, J.; Südhof, T.C. The membrane fusion enigma: SNAREs, Sec1/Munc18 proteins, and their accomplices--guilty as charged? Annu. Rev. Cell Dev. Biol.,  2012, 28, 279-308.
[http://dx.doi.org/10.1146/annurev-cellbio-101011-155818] [PMID: 23057743] 
[127] 
Liu, C.; Kershberg, L.; Wang, J.; Schneeberger, S.; Kaeser, P.S. Dopamine secretion is mediated by sparse active zone-like release sites. Cell,  2018, 172(4), 706-718.e15.
[http://dx.doi.org/10.1016/j.cell.2018.01.008] [PMID: 29398114] 
[128] 
Monti, J.M.; Monti, D. The involvement of dopamine in the modulation of sleep and waking. Sleep Med. Rev.,  2007, 11(2), 113-133.
[http://dx.doi.org/10.1016/j.smrv.2006.08.003] [PMID: 17275369] 
[129] 
Barrot, M. The ventral tegmentum and dopamine: A new wave of diversity. Neuroscience,  2014, 282, 243-247.
[http://dx.doi.org/10.1016/j.neuroscience.2014.10.017] [PMID: 25453764] 
[130] 
Solt, K.; Van Dort, C.J.; Chemali, J.J.; Taylor, N.E.; Kenny, J.D.; Brown, E.N. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology,  2014, 121(2), 311-319.
[http://dx.doi.org/10.1097/ALN.0000000000000117] [PMID: 24398816] 
[131] 
Solt, K.; Cotten, J.F.; Cimenser, A.; Wong, K.F.; Chemali, J.J.; Brown, E.N. Methylphenidate actively induces emergence from general anesthesia. Anesthesiology,  2011, 115(4), 791-803.
[http://dx.doi.org/10.1097/ALN.0b013e31822e92e5] [PMID: 21934407] 
[132] 
Chemali, J.J.; Van Dort, C.J.; Brown, E.N.; Solt, K. Active emergence from propofol general anesthesia is induced by methylphenidate. Anesthesiology,  2012, 116(5), 998-1005.
[http://dx.doi.org/10.1097/ALN.0b013e3182518bfc] [PMID: 22446983] 
[133] 
Kenny, J.D.; Taylor, N.E.; Brown, E.N.; Solt, K. Dextroamphetamine (but Not Atomoxetine) induces reanimation from general anesthesia: implications for the roles of dopamine and norepinephrine in active emergence. PLoS One,  2015, 10(7)e0131914
[http://dx.doi.org/10.1371/journal.pone.0131914] [PMID: 26148114] 
[134] 
Mantz, J.; Varlet, C.; Lecharny, J.B.; Henzel, D.; Lenot, P.; Desmonts, J.M. Effects of volatile anesthetics, thiopental, and ketamine on spontaneous and depolarization-evoked dopamine release from striatal synaptosomes in the rat. Anesthesiology,  1994, 80(2), 352-363.
[http://dx.doi.org/10.1097/00000542-199402000-00015] [PMID: 8311317] 
[135] 
Keita, H.; Henzel-Rouellé, D.; Dupont, H.; Desmonts, J.M.; Mantz, J. Halothane and isoflurane increase spontaneous but reduce the N-methyl-D-aspartate-evoked dopamine release in rat striatal slices: evidence for direct presynaptic effects. Anesthesiology,  1999, 91(6), 1788-1797.
[http://dx.doi.org/10.1097/00000542-199912000-00033] [PMID: 10598623] 
[136] 
Adachi, Y.U.; Watanabe, K.; Higuchi, H.; Satoh, T.; Zsilla, G. Halothane decreases impulse-dependent but not cytoplasmic release of dopamine from rat striatal slices. Brain Res. Bull.,  2001, 56(6), 521-524.
[http://dx.doi.org/10.1016/S0361-9230(01)00619-0] [PMID: 11786236] 
[137] 
Westphalen, R.I.; Desai, K.M.; Hemmings, H.C., Jr Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane. Br. J. Anaesth.,  2013, 110(4), 592-599.
[http://dx.doi.org/10.1093/bja/aes448] [PMID: 23213036] 
[138] 
Salord, F.; Keita, H.; Lecharny, J.B.; Henzel, D.; Desmonts, J.M.; Mantz, J. Halothane and isoflurane differentially affect the regulation of dopamine and gamma-aminobutyric acid release mediated by presynaptic acetylcholine receptors in the rat striatum. Anesthesiology,  1997, 86(3), 632-641.
[http://dx.doi.org/10.1097/00000542-199703000-00016] [PMID: 9066330] 
[139] 
Gärtner, A.; Polnau, D.G.; Staiger, V.; Sciarretta, C.; Minichiello, L.; Thoenen, H.; Bonhoeffer, T.; Korte, M. Hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase B-mediated phospholipase C gamma signaling. J. Neurosci.,  2006, 26(13), 3496-3504.
[http://dx.doi.org/10.1523/JNEUROSCI.3792-05.2006] [PMID: 16571757] 
[140] 
Jovanovic, J.N.; Czernik, A.J.; Fienberg, A.A.; Greengard, P.; Sihra, T.S. Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nat. Neurosci.,  2000, 3(4), 323-329.
[http://dx.doi.org/10.1038/73888] [PMID: 10725920] 
[141] 
Thakker-Varia, S.; Alder, J.; Crozier, R.A.; Plummer, M.R.; Black, I.B. Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels. J. Neurosci.,  2001, 21(17), 6782-6790.
[http://dx.doi.org/10.1523/JNEUROSCI.21-17-06782.2001] [PMID: 11517266] 
[142] 
Tyler, W.J.; Pozzo-Miller, L.D. BDNF enhances quantal neurotransmitter release and increases the number of docked vesicles at the active zones of hippocampal excitatory synapses. J. Neurosci.,  2001, 21(12), 4249-4258.
[http://dx.doi.org/10.1523/JNEUROSCI.21-12-04249.2001] [PMID: 11404410] 
[143] 
Tyler, W.J.; Zhang, X.L.; Hartman, K.; Winterer, J.; Muller, W.; Stanton, P.K.; Pozzo-Miller, L. BDNF increases release probability and the size of a rapidly recycling vesicle pool within rat hippocampal excitatory synapses. J. Physiol.,  2006, 574(Pt 3), 787-803.
[http://dx.doi.org/10.1113/jphysiol.2006.111310] [PMID: 16709633] 
[144] 
Pozzo-Miller, L.D.; Gottschalk, W.; Zhang, L.; McDermott, K.; Du, J.; Gopalakrishnan, R.; Oho, C.; Sheng, Z.H.; Lu, B. Impairments in high-frequency transmission, synaptic vesicle docking, and synaptic protein distribution in the hippocampus of BDNF knockout mice. J. Neurosci.,  1999, 19(12), 4972-4983.
[http://dx.doi.org/10.1523/JNEUROSCI.19-12-04972.1999] [PMID: 10366630] 
[145] 
Lin, P.Y.; Kavalali, E.T.; Monteggia, L.M. Genetic dissection of presynaptic and postsynaptic BDNF-TrkB signaling in synaptic efficacy of CA3-CA1 Synapses. Cell Rep.,  2018, 24(6), 1550-1561.
[http://dx.doi.org/10.1016/j.celrep.2018.07.020] [PMID: 30089265] 
[146] 
Kojima, M.; Takei, N.; Numakawa, T.; Ishikawa, Y.; Suzuki, S.; Matsumoto, T.; Katoh-Semba, R.; Nawa, H.; Hatanaka, H. Biological characterization and optical imaging of brain-derived neurotrophic factor-green fluorescent protein suggest an activity-dependent local release of brain-derived neurotrophic factor in neurites of cultured hippocampal neurons. J. Neurosci. Res.,  2001, 64(1), 1-10.
[http://dx.doi.org/10.1002/jnr.1080] [PMID: 11276045] 
[147] 
Matsuda, N.; Lu, H.; Fukata, Y.; Noritake, J.; Gao, H.; Mukherjee, S.; Nemoto, T.; Fukata, M.; Poo, M.M. Differential activity-dependent secretion of brain-derived neurotrophic factor from axon and dendrite. J. Neurosci.,  2009, 29(45), 14185-14198.
[http://dx.doi.org/10.1523/JNEUROSCI.1863-09.2009] [PMID: 19906967] 
[148] 
Patel, A.J.; Honoré, E.; Lesage, F.; Fink, M.; Romey, G.; Lazdunski, M. Inhalational anesthetics activate two-pore-domain background K+ channels. Nat. Neurosci.,  1999, 2(5), 422-426.
[http://dx.doi.org/10.1038/8084] [PMID: 10321245] 
[149] 
Covarrubias, M.; Barber, A.F.; Carnevale, V.; Treptow, W.; Eckenhoff, R.G. Mechanistic insights into the modulation of voltage-gated ion channels by inhalational anesthetics. Biophys. J.,  2015, 109(10), 2003-2011.
[http://dx.doi.org/10.1016/j.bpj.2015.09.032] [PMID: 26588560] 
[150] 
Steinberg, E.A.; Wafford, K.A.; Brickley, S.G.; Franks, N.P.; Wisden, W. The role of K2p channels in anaesthesia and sleep. Pflugers Arch.,  2015, 467(5), 907-916.
[http://dx.doi.org/10.1007/s00424-014-1654-4] [PMID: 25482669] 
[151] 
Yost, C.S. Potassium channels: basic aspects, functional roles, and medical significance. Anesthesiology,  1999, 90(4), 1186-1203.
[http://dx.doi.org/10.1097/00000542-199904000-00035] [PMID: 10201693] 
[152] 
Andres-Enguix, I.; Caley, A.; Yustos, R.; Schumacher, M.A.; Spanu, P.D.; Dickinson, R.; Maze, M.; Franks, N.P. Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis. J. Biol. Chem.,  2007, 282(29), 20977-20990.
[http://dx.doi.org/10.1074/jbc.M610692200] [PMID: 17548360] 
[153] 
Conway, K.E.; Cotten, J.F. Covalent modification of a volatile anesthetic regulatory site activates TASK-3 (KCNK9) tandem-pore potassium channels. Mol. Pharmacol.,  2012, 81(3), 393-400.
[http://dx.doi.org/10.1124/mol.111.076281] [PMID: 22147752] 
[154] 
Pang, D.S.; Robledo, C.J.; Carr, D.R.; Gent, T.C.; Vyssotski, A.L.; Caley, A.; Zecharia, A.Y.; Wisden, W.; Brickley, S.G.; Franks, N.P. An unexpected role for TASK-3 potassium channels in network oscillations with implications for sleep mechanisms and anesthetic action. Proc. Natl. Acad. Sci. USA,  2009, 106(41), 17546-17551.
[http://dx.doi.org/10.1073/pnas.0907228106] [PMID: 19805135] 
[155] 
Linden, A.M.; Aller, M.I.; Leppä, E.; Vekovischeva, O.; Aitta-Aho, T.; Veale, E.L.; Mathie, A.; Rosenberg, P.; Wisden, W.; Korpi, E.R. The in vivo contributions of TASK-1-containing channels to the actions of inhalation anesthetics, the alpha(2) adrenergic sedative dexmedetomidine, and cannabinoid agonists. J. Pharmacol. Exp. Ther.,  2006, 317(2), 615-626.
[http://dx.doi.org/10.1124/jpet.105.098525] [PMID: 16397088] 
[156] 
Linden, A.M.; Sandu, C.; Aller, M.I.; Vekovischeva, O.Y.; Rosenberg, P.H.; Wisden, W.; Korpi, E.R. TASK-3 knockout mice exhibit exaggerated nocturnal activity, impairments in cognitive functions, and reduced sensitivity to inhalation anesthetics. J. Pharmacol. Exp. Ther.,  2007, 323(3), 924-934.
[http://dx.doi.org/10.1124/jpet.107.129544] [PMID: 17875609] 
[157] 
Chae, Y.J.; Zhang, J.; Au, P.; Sabbadini, M.; Xie, G.X.; Yost, C.S. Discrete change in volatile anesthetic sensitivity in mice with inactivated tandem pore potassium ion channel TRESK. Anesthesiology,  2010, 113(6), 1326-1337.
[http://dx.doi.org/10.1097/ALN.0b013e3181f90ca5] [PMID: 21042202] 
[158] 
Lazarenko, R.M.; Willcox, S.C.; Shu, S.; Berg, A.P.; Jevtovic-Todorovic, V.; Talley, E.M.; Chen, X.; Bayliss, D.A. Motoneuronal TASK channels contribute to immobilizing effects of inhalational general anesthetics. J. Neurosci.,  2010, 30(22), 7691-7704.
[http://dx.doi.org/10.1523/JNEUROSCI.1655-10.2010] [PMID: 20519544] 
[159] 
Tibbs, G.R.; Rowley, T.J.; Sanford, R.L.; Herold, K.F.; Proekt, A.; Hemmings, H.C., Jr; Andersen, O.S.; Goldstein, P.A.; Flood, P.D. HCN1 channels as targets for anesthetic and nonanesthetic propofol analogs in the amelioration of mechanical and thermal hyperalgesia in a mouse model of neuropathic pain. J. Pharmacol. Exp. Ther.,  2013, 345(3), 363-373.
[http://dx.doi.org/10.1124/jpet.113.203620] [PMID: 23549867] 
[160] 
Zhou, C.; Liang, P.; Liu, J.; Ke, B.; Wang, X.; Li, F.; Li, T.; Bayliss, D.A.; Chen, X. HCN1 channels contribute to the effects of amnesia and hypnosis but not immobility of volatile anesthetics. Anesth. Analg.,  2015, 121(3), 661-666.
[http://dx.doi.org/10.1213/ANE.0000000000000830] [PMID: 26287296] 
[161] 
Gao, J.; Hu, Z.; Shi, L.; Li, N.; Ouyang, Y.; Shu, S.; Yao, S.; Chen, X. HCN channels contribute to the sensitivity of intravenous anesthetics in developmental mice. Oncotarget,  2018, 9(16), 12907-12917.
[http://dx.doi.org/10.18632/oncotarget.24408] [PMID: 29560119] 
[162] 
Antkowiak, B. In vitro networks: cortical mechanisms of anaesthetic action. Br. J. Anaesth.,  2002, 89(1), 102-111.
[http://dx.doi.org/10.1093/bja/aef154] [PMID: 12173223] 
[163] 
Linden, A.M.; Aller, M.I.; Leppä, E.; Rosenberg, P.H.; Wisden, W.; Korpi, E.R.K + channel TASK-1 knockout mice show enhanced sensitivities to ataxic and hypnotic effects of GABA(A) receptor ligands. J. Pharmacol. Exp. Ther.,  2008, 327(1), 277-286.
[http://dx.doi.org/10.1124/jpet.108.142083] [PMID: 18660435] 
[164] 
Chen, X.; Shu, S.; Bayliss, D.A. HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. J. Neurosci.,  2009, 29(3), 600-609.
[http://dx.doi.org/10.1523/JNEUROSCI.3481-08.2009] [PMID: 19158287] 
[165] 
Zhou, C.; Douglas, J.E.; Kumar, N.N.; Shu, S.; Bayliss, D.A.; Chen, X. Forebrain HCN1 channels contribute to hypnotic actions of ketamine. Anesthesiology,  2013, 118(4), 785-795.
[http://dx.doi.org/10.1097/ALN.0b013e318287b7c8] [PMID: 23377220] 
[166] 
Chen, Y.A.; Scheller, R.H. SNARE-mediated membrane fusion. Nat. Rev. Mol. Cell Biol.,  2001, 2(2), 98-106.
[http://dx.doi.org/10.1038/35052017] [PMID: 11252968] 
[167] 
Chen, Y.A.; Scales, S.J.; Scheller, R.H. Sequential SNARE assembly underlies priming and triggering of exocytosis. Neuron,  2001, 30(1), 161-170.
[http://dx.doi.org/10.1016/S0896-6273(01)00270-7] [PMID: 11343652] 
[168] 
Söllner, T.; Bennett, M.K.; Whiteheart, S.W.; Scheller, R.H.; Rothman, J.E. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell,  1993, 75(3), 409-418.
[http://dx.doi.org/10.1016/0092-8674(93)90376-2] [PMID: 8221884] 
[169] 
Hawasli, A.H.; Saifee, O.; Liu, C.; Nonet, M.L.; Crowder, C.M. Resistance to volatile anesthetics by mutations enhancing excitatory neurotransmitter release in Caenorhabditis elegans. Genetics,  2004, 168(2), 831-843.
[http://dx.doi.org/10.1534/genetics.104.030502] [PMID: 15514057] 
[170] 
Zalucki, O.H.; Menon, H.; Kottler, B.; Faville, R.; Day, R.; Bademosi, A.T.; Lavidis, N.; Karunanithi, S.; van Swinderen, B. Syntaxin1A-mediated resistance and hypersensitivity to isoflurane in drosophila melanogaster. Anesthesiology,  2015, 122(5), 1060-1074.
[http://dx.doi.org/10.1097/ALN.0000000000000629] [PMID: 25738637] 
[171] 
Nagele, P.; Mendel, J.B.; Placzek, W.J.; Scott, B.A.; D’Avignon, D.A.; Crowder, C.M. Volatile anesthetics bind rat synaptic snare proteins. Anesthesiology,  2005, 103(4), 768-778.
[http://dx.doi.org/10.1097/00000542-200510000-00015] [PMID: 16192769] 
[172] 
Herring, B.E.; Xie, Z.; Marks, J.; Fox, A.P. Isoflurane inhibits the neurotransmitter release machinery. J. Neurophysiol.,  2009, 102(2), 1265-1273.
[http://dx.doi.org/10.1152/jn.00252.2009] [PMID: 19515956] 
[173] 
Xie, Z.; McMillan, K.; Pike, C.M.; Cahill, A.L.; Herring, B.E.; Wang, Q.; Fox, A.P. Interaction of anesthetics with neurotransmitter release machinery proteins. J. Neurophysiol.,  2013, 109(3), 758-767.
[http://dx.doi.org/10.1152/jn.00666.2012] [PMID: 23136341] 
[174] 
Bademosi, A.T.; Steeves, J.; Karunanithi, S.; Zalucki, O.H.; Gormal, R.S.; Liu, S.; Lauwers, E.; Verstreken, P.; Anggono, V.; Meunier, F.A.; van Swinderen, B. Trapping of syntaxin1a in presynaptic nanoclusters by a clinically relevant general anesthetic. Cell Rep.,  2018, 22(2), 427-440.
[http://dx.doi.org/10.1016/j.celrep.2017.12.054] [PMID: 29320738] 
[175] 
Herring, B.E.; McMillan, K.; Pike, C.M.; Marks, J.; Fox, A.P.; Xie, Z. Etomidate and propofol inhibit the neurotransmitter release machinery at different sites. J. Physiol.,  2011, 589(Pt 5), 1103-1115.
[http://dx.doi.org/10.1113/jphysiol.2010.200964] [PMID: 21173083] 
[176] 
Spray, D.C.; Duffy, H.S.; Scemes, E. Gap junctions in glia. Types, roles, and plasticity. Adv. Exp. Med. Biol.,  1999, 468, 339-359.
[http://dx.doi.org/10.1007/978-1-4615-4685-6_27] [PMID: 10635041] 
[177] 
Johnston, M.F.; Simon, S.A.; Ramón, F. Interaction of anaesthetics with electrical synapses. Nature,  1980, 286(5772), 498-500.
[http://dx.doi.org/10.1038/286498a0] [PMID: 6250068] 
[178] 
Mantz, J.; Cordier, J.; Giaume, C. Effects of general anesthetics on intercellular communications mediated by gap junctions between astrocytes in primary culture. Anesthesiology,  1993, 78(5), 892-901.
[http://dx.doi.org/10.1097/00000542-199305000-00014] [PMID: 7683851] 
[179] 
Wentlandt, K.; Carlen, P.L.; Kushnir, M.; Naus, C.C.; El-Beheiry, H. General anesthetics attenuate gap junction coupling in P19 cell line. J. Neurosci. Res.,  2005, 81(5), 746-752.
[http://dx.doi.org/10.1002/jnr.20577] [PMID: 15971264] 
[180] 
Masaki, E.; Kawamura, M.; Kato, F. Attenuation of gap-junction-mediated signaling facilitated anesthetic effect of sevoflurane in the central nervous system of rats. Anesth. Analg.,  2004, 98(3), 647-652.
[http://dx.doi.org/10.1213/01.ANE.0000103259.72635.72] [PMID: 14980913] 
[181] 
Wentlandt, K.; Samoilova, M.; Carlen, P.L.; El Beheiry, H. General anesthetics inhibit gap junction communication in cultured organotypic hippocampal slices. Anesth. Analg.,  2006, 102(6), 1692-1698.
[http://dx.doi.org/10.1213/01.ane.0000202472.41103.78] [PMID: 16717311] 
[182] 
Jacobson, G.M.; Voss, L.J.; Melin, S.M.; Cursons, R.T.; Sleigh, J.W. The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice. Anaesthesia,  2011, 66(5), 361-367.
[http://dx.doi.org/10.1111/j.1365-2044.2011.06658.x] [PMID: 21418043] 
[183] 
Rudolph, U.; Antkowiak, B. Molecular and neuronal substrates for general anaesthetics. Nat. Rev. Neurosci.,  2004, 5(9), 709-720.
[http://dx.doi.org/10.1038/nrn1496] [PMID: 15322529] 
[184] 
Allison, D.W.; Gelfand, V.I.; Spector, I.; Craig, A.M. Role of actin in anchoring postsynaptic receptors in cultured hippocampal neurons: differential attachment of NMDA versus AMPA receptors. J. Neurosci.,  1998, 18(7), 2423-2436.
[http://dx.doi.org/10.1523/JNEUROSCI.18-07-02423.1998] [PMID: 9502803] 
[185] 
van Rossum, D.; Hanisch, U.K. Cytoskeletal dynamics in dendritic spines: direct modulation by glutamate receptors? Trends Neurosci.,  1999, 22(7), 290-295.
[http://dx.doi.org/10.1016/S0166-2236(99)01404-6] [PMID: 10370249] 
[186] 
Kaech, S.; Brinkhaus, H.; Matus, A. Volatile anesthetics block actin-based motility in dendritic spines. Proc. Natl. Acad. Sci. USA,  1999, 96(18), 10433-10437.
[http://dx.doi.org/10.1073/pnas.96.18.10433] [PMID: 10468626] 
[187] 
Hirota, K.; Roth, S.H. Sevoflurane modulates both GABAA and GABAB receptors in area CA1 of rat hippocampus. Br. J. Anaesth.,  1997, 78(1), 60-65.
[http://dx.doi.org/10.1093/bja/78.1.60] [PMID: 9059206] 
[188] 
Antkowiak, B. Different actions of general anesthetics on the firing patterns of neocortical neurons mediated by the GABA(A) receptor. Anesthesiology,  1999, 91(2), 500-511.
[http://dx.doi.org/10.1097/00000542-199908000-00025] [PMID: 10443614] 
[189] 
Nishikawa, K.; MacIver, M.B. Agent-selective effects of volatile anesthetics on GABAA receptor-mediated synaptic inhibition in hippocampal interneurons. Anesthesiology,  2001, 94(2), 340-347.
[http://dx.doi.org/10.1097/00000542-200102000-00025] [PMID: 11176100] 
[190] 
Kitamura, A.; Sato, R.; Marszalec, W.; Yeh, J.Z.; Ogawa, R.; Narahashi, T. Halothane and propofol modulation of gamma-aminobutyric acidA receptor single-channel currents. Anesth. Analg.,  2004, 99(2), 409-415.
[http://dx.doi.org/10.1213/01.ANE.0000131969.46439.71] [PMID: 15271715] 
[191] 
Hentschke, H.; Schwarz, C.; Antkowiak, B. Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor-mediated inhibition. Eur. J. Neurosci.,  2005, 21(1), 93-102.
[http://dx.doi.org/10.1111/j.1460-9568.2004.03843.x] [PMID: 15654846] 
[192] 
Olsen, R.W.; Tobin, A.J. Molecular biology of GABAA receptors. FASEB J.,  1990, 4(5), 1469-1480.
[http://dx.doi.org/10.1096/fasebj.4.5.2155149] [PMID: 2155149] 
[193] 
Sieghart, W. GABAA receptors: ligand-gated Cl- ion channels modulated by multiple drug-binding sites. Trends Pharmacol. Sci.,  1992, 13(12), 446-450.
[http://dx.doi.org/10.1016/0165-6147(92)90142-S] [PMID: 1338138] 
[194] 
Garcia, P.S.; Kolesky, S.E.; Jenkins, A. General anesthetic actions on GABA(A) receptors. Curr. Neuropharmacol.,  2010, 8(1), 2-9.
[http://dx.doi.org/10.2174/157015910790909502] [PMID: 20808541] 
[195] 
Nakahiro, M.; Yeh, J.Z.; Brunner, E.; Narahashi, T. General anesthetics modulate GABA receptor channel complex in rat dorsal root ganglion neurons. FASEB J.,  1989, 3(7), 1850-1854.
[http://dx.doi.org/10.1096/fasebj.3.7.2541038] [PMID: 2541038] 
[196] 
Wakamori, M.; Ikemoto, Y.; Akaike, N. Effects of two volatile anesthetics and a volatile convulsant on the excitatory and inhibitory amino acid responses in dissociated CNS neurons of the rat. J. Neurophysiol.,  1991, 66(6), 2014-2021.
[http://dx.doi.org/10.1152/jn.1991.66.6.2014] [PMID: 1667416] 
[197] 
Jones, M.V.; Brooks, P.A.; Harrison, N.L. Enhancement of gamma-aminobutyric acid-activated Cl- currents in cultured rat hippocampal neurones by three volatile anaesthetics. J. Physiol.,  1992, 449, 279-293.
[http://dx.doi.org/10.1113/jphysiol.1992.sp019086] [PMID: 1326046] 
[198] 
Li, X.; Czajkowski, C.; Pearce, R.A. Rapid and direct modulation of GABAA receptors by halothane. Anesthesiology,  2000, 92(5), 1366-1375.
[http://dx.doi.org/10.1097/00000542-200005000-00027] [PMID: 10781283] 
[199] 
Hales, T.G.; Lambert, J.J. The actions of propofol on inhibitory amino acid receptors of bovine adrenomedullary chromaffin cells and rodent central neurones. Br. J. Pharmacol.,  1991, 104(3), 619-628.
[http://dx.doi.org/10.1111/j.1476-5381.1991.tb12479.x] [PMID: 1665745] 
[200] 
Uchida, I.; Kamatchi, G.; Burt, D.; Yang, J. Etomidate potentiation of GABAA receptor gated current depends on the subunit composition. Neurosci. Lett.,  1995, 185(3), 203-206.
[http://dx.doi.org/10.1016/0304-3940(95)11263-V] [PMID: 7753491] 
[201] 
Olsen, R.W.; Yang, J.; King, R.G.; Dilber, A.; Stauber, G.B.; Ransom, R.W. Barbiturate and benzodiazepine modulation of GABA receptor binding and function. Life Sci.,  1986, 39(21), 1969-1976.
[http://dx.doi.org/10.1016/0024-3205(86)90320-6] [PMID: 2431244] 
[202] 
Olsen, R.W.; Sapp, D.M.; Bureau, M.H.; Turner, D.M.; Kokka, N. Allosteric actions of central nervous system depressants including anesthetics on subtypes of the inhibitory gamma-aminobutyric acidA receptor-chloride channel complex. Ann. N. Y. Acad. Sci.,  1991, 625, 145-154.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb33838.x] [PMID: 1711804] 
[203] 
Zhang, Y.; Stabernack, C.; Sonner, J.; Dutton, R.; Eger, E.I. II Both cerebral GABA(A) receptors and spinal GABA(A) receptors modulate the capacity of isoflurane to produce immobility. Anesth. Analg.,  2001, 92(6), 1585-1589.
[http://dx.doi.org/10.1097/00000539-200106000-00047] [PMID: 11375851] 
[204] 
Lam, D.W.; Reynolds, J.N. Modulatory and direct effects of propofol on recombinant GABAA receptors expressed in xenopus oocytes: influence of alpha- and gamma2-subunits. Brain Res.,  1998, 784(1-2), 179-187.
[http://dx.doi.org/10.1016/S0006-8993(97)01334-6] [PMID: 9518600] 
[205] 
Hara, M.; Kai, Y.; Ikemoto, Y. Propofol activates GABAA receptor-chloride ionophore complex in dissociated hippocampal pyramidal neurons of the rat. Anesthesiology,  1993, 79(4), 781-788.
[http://dx.doi.org/10.1097/00000542-199310000-00021] [PMID: 8214758] 
[206] 
Hara, M.; Kai, Y.; Ikemoto, Y. Enhancement by propofol of the gamma-aminobutyric acidA response in dissociated hippocampal pyramidal neurons of the rat. Anesthesiology,  1994, 81(4), 988-994.
[http://dx.doi.org/10.1097/00000542-199410000-00026] [PMID: 7943850] 
[207] 
Orser, B.A.; Wang, L.Y.; Pennefather, P.S.; MacDonald, J.F. Propofol modulates activation and desensitization of GABAA receptors in cultured murine hippocampal neurons. J. Neurosci.,  1994, 14(12), 7747-7760.
[http://dx.doi.org/10.1523/JNEUROSCI.14-12-07747.1994] [PMID: 7996209] 
[208] 
Bai, D.; Pennefather, P.S.; MacDonald, J.F.; Orser, B.A. The general anesthetic propofol slows deactivation and desensitization of GABA(A) receptors. J. Neurosci.,  1999, 19(24), 10635-10646.
[http://dx.doi.org/10.1523/JNEUROSCI.19-24-10635.1999] [PMID: 10594047] 
[209] 
Adodra, S.; Hales, T.G. Potentiation, activation and blockade of GABAA receptors of clonal murine hypothalamic GT1-7 neurones by propofol. Br. J. Pharmacol.,  1995, 115(6), 953-960.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb15903.x] [PMID: 7582526] 
[210] 
Thyagarajan, R.; Ramanjaneyulu, R.; Ticku, M.K. Enhancement of diazepam and gamma-aminobutyric acid binding by (+)etomidate and pentobarbital. J. Neurochem.,  1983, 41(2), 578-585.
[http://dx.doi.org/10.1111/j.1471-4159.1983.tb04778.x] [PMID: 6308164] 
[211] 
Ashton, D.; Wauquier, A. Modulation of a GABA-ergic inhibitory circuit in the in vitro hippocampus by etomidate isomers. Anesth. Analg.,  1985, 64(10), 975-980.
[http://dx.doi.org/10.1213/00000539-198510000-00006] [PMID: 2994524] 
[212] 
Proctor, W.R.; Mynlieff, M.; Dunwiddie, T.V. Facilitatory action of etomidate and pentobarbital on recurrent inhibition in rat hippocampal pyramidal neurons. J. Neurosci.,  1986, 6(11), 3161-3168.
[http://dx.doi.org/10.1523/JNEUROSCI.06-11-03161.1986] [PMID: 3772427] 
[213] 
Yang, J.; Uchida, I. Mechanisms of etomidate potentiation of GABAA receptor-gated currents in cultured postnatal hippocampal neurons. Neuroscience,  1996, 73(1), 69-78.
[http://dx.doi.org/10.1016/0306-4522(96)00018-8] [PMID: 8783230] 
[214] 
Delgado-Lezama, R.; Loeza-Alcocer, E.; Andrés, C.; Aguilar, J.; Guertin, P.A.; Felix, R. Extrasynaptic GABA(A) receptors in the brainstem and spinal cord: structure and function. Curr. Pharm. Des.,  2013, 19(24), 4485-4497.
[http://dx.doi.org/10.2174/1381612811319240013] [PMID: 23360278] 
[215] 
Kotani, N.; Akaike, N. The effects of volatile anesthetics on synaptic and extrasynaptic GABA-induced neurotransmission. Brain Res. Bull.,  2013, 93, 69-79.
[http://dx.doi.org/10.1016/j.brainresbull.2012.08.001] [PMID: 22925739] 
[216] 
Topf, N.; Jenkins, A.; Baron, N.; Harrison, N.L. Effects of isoflurane on gamma-aminobutyric acid type A receptors activated by full and partial agonists. Anesthesiology,  2003, 98(2), 306-311.
[http://dx.doi.org/10.1097/00000542-200302000-00007] [PMID: 12552186] 
[217] 
Olsen, R.W.; Li, G.D. GABA(A) receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation. Can. J. Anaesth.,  2011, 58(2), 206-215.
[http://dx.doi.org/10.1007/s12630-010-9429-7] [PMID: 21194017] 
[218] 
Bai, D.; Zhu, G.; Pennefather, P.; Jackson, M.F.; MacDonald, J.F.; Orser, B.A. Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons. Mol. Pharmacol.,  2001, 59(4), 814-824.
[http://dx.doi.org/10.1124/mol.59.4.814] [PMID: 11259626] 
[219] 
Burt, D.R.; Kamatchi, G.L. GABAA receptor subtypes: from pharmacology to molecular biology. FASEB J.,  1991, 5(14), 2916-2923.
[http://dx.doi.org/10.1096/fasebj.5.14.1661244] [PMID: 1661244] 
[220] 
Macdonald, R.L.; Olsen, R.W. GABAA receptor channels. Annu. Rev. Neurosci.,  1994, 17, 569-602.
[http://dx.doi.org/10.1146/annurev.ne.17.030194.003033] [PMID: 7516126] 
[221] 
Ogurusu, T.; Shingai, R. Cloning of a putative gamma-aminobutyric acid (GABA) receptor subunit rho 3 cDNA. Biochim. Biophys. Acta,  1996, 1305(1-2), 15-18.
[http://dx.doi.org/10.1016/0167-4781(95)00205-7] [PMID: 8605242] 
[222] 
Horne, A.L.; Harkness, P.C.; Hadingham, K.L.; Whiting, P.; Kemp, J.A. The influence of the gamma 2L subunit on the modulation of responses to GABAA receptor activation. Br. J. Pharmacol.,  1993, 108(3), 711-716.
[http://dx.doi.org/10.1111/j.1476-5381.1993.tb12866.x] [PMID: 8385534] 
[223] 
Blair, L.A.; Levitan, E.S.; Marshall, J.; Dionne, V.E.; Barnard, E.A. Single subunits of the GABAA receptor form ion channels with properties of the native receptor. Science,  1988, 242(4878), 577-579.
[http://dx.doi.org/10.1126/science.2845583] [PMID: 2845583] 
[224] 
Sigel, E.; Baur, R.; Trube, G.; Möhler, H.; Malherbe, P. The effect of subunit composition of rat brain GABAA receptors on channel function. Neuron,  1990, 5(5), 703-711.
[http://dx.doi.org/10.1016/0896-6273(90)90224-4] [PMID: 1699569] 
[225] 
Angelotti, T.P.; Macdonald, R.L. Assembly of GABAA receptor subunits: alpha 1 beta 1 and alpha 1 beta 1 gamma 2S subunits produce unique ion channels with dissimilar single-channel properties. J. Neurosci.,  1993, 13(4), 1429-1440.
[http://dx.doi.org/10.1523/JNEUROSCI.13-04-01429.1993] [PMID: 7681870] 
[226] 
Im, H.K.; Im, W.B.; Carter, D.B.; McKinley, D.D. Interaction of beta-carboline inverse agonists for the benzodiazepine site with another site on GABAA receptors. Br. J. Pharmacol.,  1995, 114(5), 1040-1044.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb13310.x] [PMID: 7780638] 
[227] 
Chang, Y.; Wang, R.; Barot, S.; Weiss, D.S. Stoichiometry of a recombinant GABAA receptor. J. Neurosci.,  1996, 16(17), 5415-5424.
[http://dx.doi.org/10.1523/JNEUROSCI.16-17-05415.1996] [PMID: 8757254] 
[228] 
Lolait, S.J.; O’Carroll, A.M.; Kusano, K.; Mahan, L.C. Pharmacological characterization and region-specific expression in brain of the beta 2- and beta 3-subunits of the rat GABAA receptor. FEBS Lett.,  1989, 258(1), 17-21.
[http://dx.doi.org/10.1016/0014-5793(89)81605-9] [PMID: 2556296] 
[229] 
Ymer, S.; Schofield, P.R.; Draguhn, A.; Werner, P.; Köhler, M.; Seeburg, P.H. GABAA receptor beta subunit heterogeneity: functional expression of cloned cDNAs. EMBO J.,  1989, 8(6), 1665-1670.
[http://dx.doi.org/10.1002/j.1460-2075.1989.tb03557.x] [PMID: 2548852] 
[230] 
Valeyev, A.Y.; Barker, J.L.; Cruciani, R.A.; Lange, G.D.; Smallwood, V.V.; Mahan, L.C. Characterization of the gamma-aminobutyric acidA receptor-channel complex composed of alpha 1 beta 2 and alpha 1 beta 3 subunits from rat brain. J. Pharmacol. Exp. Ther.,  1993, 265(2), 985-991.
[PMID: 8388463] 
[231] 
Liu, K.; Jounaidi, Y.; Forman, S.A.; Feng, H.J. Etomidate uniquely modulates the desensitization of recombinant α1β3δ GABA(A) receptors. Neuroscience,  2015, 300, 307-313.
[http://dx.doi.org/10.1016/j.neuroscience.2015.05.051] [PMID: 26028470] 
[232] 
Pritchett, D.B.; Sontheimer, H.; Shivers, B.D.; Ymer, S.; Kettenmann, H.; Schofield, P.R.; Seeburg, P.H. Importance of a novel GABAA receptor subunit for benzodiazepine pharmacology. Nature,  1989, 338(6216), 582-585.
[http://dx.doi.org/10.1038/338582a0] [PMID: 2538761] 
[233] 
Jones, M.V.; Harrison, N.L.; Pritchett, D.B.; Hales, T.G. Modulation of the GABAA receptor by propofol is independent of the gamma subunit. J. Pharmacol. Exp. Ther.,  1995, 274(2), 962-968.
[PMID: 7636760] 
[234] 
Sigel, E.; Baur, R.; Malherbe, P.; Möhler, H. The rat beta 1-subunit of the GABAA receptor forms a picrotoxin-sensitive anion channel open in the absence of GABA. FEBS Lett.,  1989, 257(2), 377-379.
[http://dx.doi.org/10.1016/0014-5793(89)81576-5] [PMID: 2479580] 
[235] 
Krishek, B.J.; Moss, S.J.; Smart, T.G. Homomeric beta 1 gamma-aminobutyric acid A receptor-ion channels: evaluation of pharmacological and physiological properties. Mol. Pharmacol.,  1996, 49(3), 494-504.
[PMID: 8643089] 
[236] 
Cestari, I.N.; Uchida, I.; Li, L.; Burt, D.; Yang, J. The agonistic action of pentobarbital on GABAA beta-subunit homomeric receptors. Neuroreport,  1996, 7(4), 943-947.
[http://dx.doi.org/10.1097/00001756-199603220-00023] [PMID: 8724679] 
[237] 
Davies, P.A.; Hanna, M.C.; Hales, T.G.; Kirkness, E.F. Insensitivity to anaesthetic agents conferred by a class of GABA(A) receptor subunit. Nature,  1997, 385(6619), 820-823.
[http://dx.doi.org/10.1038/385820a0] [PMID: 9039914] 
[238] 
Sanna, E.; Garau, F.; Harris, R.A. Novel properties of homomeric beta 1 gamma-aminobutyric acid type A receptors: actions of the anesthetics propofol and pentobarbital. Mol. Pharmacol.,  1995, 47(2), 213-217.
[PMID: 7870027] 
[239] 
Williams, D.B.; Akabas, M.H. Structural evidence that propofol stabilizes different GABA(A) receptor states at potentiating and activating concentrations. J. Neurosci.,  2002, 22(17), 7417-7424.
[http://dx.doi.org/10.1523/JNEUROSCI.22-17-07417.2002] [PMID: 12196563] 
[240] 
Krasowski, M.D.; Koltchine, V.V.; Rick, C.E.; Ye, Q.; Finn, S.E.; Harrison, N.L. Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane. Mol. Pharmacol.,  1998, 53(3), 530-538.
[http://dx.doi.org/10.1124/mol.53.3.530] [PMID: 9495821] 
[241] 
Siegwart, R.; Jurd, R.; Rudolph, U. Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3)gamma(2)gamma-aminobutyric acid(A) receptors. J. Neurochem.,  2002, 80(1), 140-148.
[http://dx.doi.org/10.1046/j.0022-3042.2001.00682.x] [PMID: 11796752] 
[242] 
Lor, C.; Perouansky, M.; Pearce, R.A. Isoflurane potentiation of GABAA receptors is reduced but not eliminated by the β3(n265m) mutation. Int. J. Mol. Sci.,  2020, 21(24)E9534
[http://dx.doi.org/10.3390/ijms21249534] [PMID: 33333797] 
[243] 
Drexler, B.; Jurd, R.; Rudolph, U.; Antkowiak, B. Distinct actions of etomidate and propofol at beta3-containing gamma-aminobutyric acid type A receptors. Neuropharmacology,  2009, 57(4), 446-455.
[http://dx.doi.org/10.1016/j.neuropharm.2009.06.014] [PMID: 19555700] 
[244] 
Jurd, R.; Arras, M.; Lambert, S.; Drexler, B.; Siegwart, R.; Crestani, F.; Zaugg, M.; Vogt, K.E.; Ledermann, B.; Antkowiak, B.; Rudolph, U. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA(A) receptor beta3 subunit. FASEB J.,  2003, 17(2), 250-252.
[http://dx.doi.org/10.1096/fj.02-0611fje] [PMID: 12475885] 
[245] 
Reynolds, D.S.; Rosahl, T.W.; Cirone, J.; O’Meara, G.F.; Haythornthwaite, A.; Newman, R.J.; Myers, J.; Sur, C.; Howell, O.; Rutter, A.R.; Atack, J.; Macaulay, A.J.; Hadingham, K.L.; Hutson, P.H.; Belelli, D.; Lambert, J.J.; Dawson, G.R.; McKernan, R.; Whiting, P.J.; Wafford, K.A. Sedation and anesthesia mediated by distinct GABA(A) receptor isoforms. J. Neurosci.,  2003, 23(24), 8608-8617.
[http://dx.doi.org/10.1523/JNEUROSCI.23-24-08608.2003] [PMID: 13679430] 
[246] 
O’Meara, G.F.; Newman, R.J.; Fradley, R.L.; Dawson, G.R.; Reynolds, D.S. The GABA-A beta3 subunit mediates anaesthesia induced by etomidate. Neuroreport,  2004, 15(10), 1653-1656.
[http://dx.doi.org/10.1097/01.wnr.0000134842.56131.fe] [PMID: 15232301] 
[247] 
Carlson, B.X.; Belhage, B.; Hansen, G.H.; Elster, L.; Olsen, R.W.; Schousboe, A. Expression of the GABA(A) receptor alpha6 subunit in cultured cerebellar granule cells is developmentally regulated by activation of GABA(A) receptors. J. Neurosci. Res.,  1997, 50(6), 1053-1062.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19971215)50:6<1053:AID-JNR17>3.0.CO;2-5] [PMID: 9452021] 
[248] 
Quinlan, J.J.; Homanics, G.E.; Firestone, L.L. Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor. Anesthesiology,  1998, 88(3), 775-780.
[http://dx.doi.org/10.1097/00000542-199803000-00030] [PMID: 9523823] 
[249] 
Lambert, S.; Arras, M.; Vogt, K.E.; Rudolph, U. Isoflurane-induced surgical tolerance mediated only in part by beta3-containing GABA(A) receptors. Eur. J. Pharmacol.,  2005, 516(1), 23-27.
[http://dx.doi.org/10.1016/j.ejphar.2005.04.030] [PMID: 15913600] 
[250] 
Liao, M.; Sonner, J.M.; Husain, S.S.; Miller, K.W.; Jurd, R.; Rudolph, U.; Eger, E.I. II R (+) etomidate and the photoactivable R (+) azietomidate have comparable anesthetic activity in wild-type mice and comparably decreased activity in mice with a N265M point mutation in the gamma-aminobutyric acid receptor beta3 subunit. Anesth. Analg.,  2005, 101(1), 131-135.
[http://dx.doi.org/10.1213/01.ANE.0000153011.64764.6F] [PMID: 15976219] 
[251] 
Akeju, O.; Hamilos, A.E.; Song, A.H.; Pavone, K.J.; Purdon, P.L.; Brown, E.N. GABAA circuit mechanisms are associated with ether anesthesia-induced unconsciousness. Clin. Neurophysiol.,  2016, 127(6), 2472-2481.
[http://dx.doi.org/10.1016/j.clinph.2016.02.012] [PMID: 27178867] 
[252] 
Rajendra, S.; Vandenberg, R.J.; Pierce, K.D.; Cunningham, A.M.; French, P.W.; Barry, P.H.; Schofield, P.R. The unique extracellular disulfide loop of the glycine receptor is a principal ligand binding element. EMBO J.,  1995, 14(13), 2987-2998.
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb07301.x] [PMID: 7621814] 
[253] 
Birnir, B.; Tierney, M.L.; Lim, M.; Cox, G.B.; Gage, P.W. Nature of the 5′ residue in the M2 domain affects function of the human alpha 1 beta 1 GABAA receptor. Synapse,  1997, 26(3), 324-327.
[http://dx.doi.org/10.1002/(SICI)1098-2396(199707)26:3<324:AID-SYN13>3.0.CO;2-V] [PMID: 9183821] 
[254] 
Krasowski, M.D.; Nishikawa, K.; Nikolaeva, N.; Lin, A.; Harrison, N.L. Methionine 286 in transmembrane domain 3 of the GABAA receptor beta subunit controls a binding cavity for propofol and other alkylphenol general anesthetics. Neuropharmacology,  2001, 41(8), 952-964.
[http://dx.doi.org/10.1016/S0028-3908(01)00141-1] [PMID: 11747900] 
[255] 
Bali, M.; Akabas, M.H. Defining the propofol binding site location on the GABAA receptor. Mol. Pharmacol.,  2004, 65(1), 68-76.
[http://dx.doi.org/10.1124/mol.65.1.68] [PMID: 14722238] 
[256] 
Chang, C.S.; Olcese, R.; Olsen, R.W. A single M1 residue in the beta2 subunit alters channel gating of GABAA receptor in anesthetic modulation and direct activation. J. Biol. Chem.,  2003, 278(44), 42821-42828.
[http://dx.doi.org/10.1074/jbc.M306978200] [PMID: 12939268] 
[257] 
Mihic, S.J.; Ye, Q.; Wick, M.J.; Koltchine, V.V.; Krasowski, M.D.; Finn, S.E.; Mascia, M.P.; Valenzuela, C.F.; Hanson, K.K.; Greenblatt, E.P.; Harris, R.A.; Harrison, N.L. Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors. Nature,  1997, 389(6649), 385-389.
[http://dx.doi.org/10.1038/38738] [PMID: 9311780] 
[258] 
Werner, D.F.; Swihart, A.; Rau, V.; Jia, F.; Borghese, C.M.; McCracken, M.L.; Iyer, S.; Fanselow, M.S.; Oh, I.; Sonner, J.M.; Eger, E.I., II; Harrison, N.L.; Harris, R.A.; Homanics, G.E. Inhaled anesthetic responses of recombinant receptors and knockin mice harboring α2(S270H/L277A) GABA(A) receptor subunits that are resistant to isoflurane. J. Pharmacol. Exp. Ther.,  2011, 336(1), 134-144.
[http://dx.doi.org/10.1124/jpet.110.170431] [PMID: 20807777] 
[259] 
Nishikawa, K.; Jenkins, A.; Paraskevakis, I.; Harrison, N.L. Volatile anesthetic actions on the GABAA receptors: contrasting effects of alpha 1(S270) and beta 2(N265) point mutations. Neuropharmacology,  2002, 42(3), 337-345.
[http://dx.doi.org/10.1016/S0028-3908(01)00189-7] [PMID: 11897112] 
[260] 
Sonner, J.M.; Werner, D.F.; Elsen, F.P.; Xing, Y.; Liao, M.; Harris, R.A.; Harrison, N.L.; Fanselow, M.S.; Eger, E.I., II; Homanics, G.E. Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane. Anesthesiology,  2007, 106(1), 107-113.
[http://dx.doi.org/10.1097/00000542-200701000-00019] [PMID: 17197852] 
[261] 
Ying, S.W.; Werner, D.F.; Homanics, G.E.; Harrison, N.L.; Goldstein, P.A. Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms. Neuropharmacology,  2009, 56(2), 438-447.
[http://dx.doi.org/10.1016/j.neuropharm.2008.09.015] [PMID: 18948126] 
[262] 
Rau, V.; Iyer, S.V.; Oh, I.; Chandra, D.; Harrison, N.; Eger, E.I., II; Fanselow, M.S.; Homanics, G.E.; Sonner, J.M. Gamma-aminobutyric acid type A receptor alpha 4 subunit knockout mice are resistant to the amnestic effect of isoflurane. Anesth. Analg.,  2009, 109(6), 1816-1822.
[http://dx.doi.org/10.1213/ANE.0b013e3181bf6ae6] [PMID: 19923508] 
[263] 
Sun, C.; Sieghart, W.; Kapur, J. Distribution of alpha1, alpha4, gamma2, and delta subunits of GABAA receptors in hippocampal granule cells. Brain Res.,  2004, 1029(2), 207-216.
[http://dx.doi.org/10.1016/j.brainres.2004.09.056] [PMID: 15542076] 
[264] 
Benkwitz, C.; Banks, M.I.; Pearce, R.A. Influence of GABAA receptor gamma2 splice variants on receptor kinetics and isoflurane modulation. Anesthesiology,  2004, 101(4), 924-936.
[http://dx.doi.org/10.1097/00000542-200410000-00018] [PMID: 15448526] 
[265] 
Caraiscos, V.B.; Newell, J.G.; You-Ten, K.E.; Elliott, E.M.; Rosahl, T.W.; Wafford, K.A.; MacDonald, J.F.; Orser, B.A. Selective enhancement of tonic GABAergic inhibition in murine hippocampal neurons by low concentrations of the volatile anesthetic isoflurane. J. Neurosci.,  2004, 24(39), 8454-8458.
[http://dx.doi.org/10.1523/JNEUROSCI.2063-04.2004] [PMID: 15456818] 
[266] 
Cheng, V.Y.; Martin, L.J.; Elliott, E.M.; Kim, J.H.; Mount, H.T.; Taverna, F.A.; Roder, J.C.; Macdonald, J.F.; Bhambri, A.; Collinson, N.; Wafford, K.A.; Orser, B.A. Alpha5GABAA receptors mediate the amnestic but not sedative-hypnotic effects of the general anesthetic etomidate. J. Neurosci.,  2006, 26(14), 3713-3720.
[http://dx.doi.org/10.1523/JNEUROSCI.5024-05.2006] [PMID: 16597725] 
[267] 
Bieda, M.C.; Su, H.; Maciver, M.B. Anesthetics discriminate between tonic and phasic gamma-aminobutyric acid receptors on hippocampal CA1 neurons. Anesth. Analg.,  2009, 108(2), 484-490.
[http://dx.doi.org/10.1213/ane.0b013e3181904571] [PMID: 19151276] 
[268] 
Ogawa, S.K.; Tanaka, E.; Shin, M.C.; Kotani, N.; Akaike, N. Volatile anesthetic effects on isolated GABA synapses and extrasynaptic receptors. Neuropharmacology,  2011, 60(4), 701-710.
[http://dx.doi.org/10.1016/j.neuropharm.2010.11.016] [PMID: 21111749] 
[269] 
Dai, S.; Perouansky, M.; Pearce, R.A. Isoflurane enhances both fast and slow synaptic inhibition in the hippocampus at amnestic concentrations. Anesthesiology,  2012, 116(4), 816-823.
[http://dx.doi.org/10.1097/ALN.0b013e31824be0e3] [PMID: 22343472] 
[270] 
Collinson, N.; Kuenzi, F.M.; Jarolimek, W.; Maubach, K.A.; Cothliff, R.; Sur, C.; Smith, A.; Otu, F.M.; Howell, O.; Atack, J.R.; McKernan, R.M.; Seabrook, G.R.; Dawson, G.R.; Whiting, P.J.; Rosahl, T.W. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor. J. Neurosci.,  2002, 22(13), 5572-5580.
[http://dx.doi.org/10.1523/JNEUROSCI.22-13-05572.2002] [PMID: 12097508] 
[271] 
Ortells, M.O.; Lunt, G.G. Evolutionary history of the ligand-gated ion-channel superfamily of receptors. Trends Neurosci.,  1995, 18(3), 121-127.
[http://dx.doi.org/10.1016/0166-2236(95)93887-4] [PMID: 7754520] 
[272] 
Tassonyi, E.; Charpantier, E.; Muller, D.; Dumont, L.; Bertrand, D. The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia. Brain Res. Bull.,  2002, 57(2), 133-150.
[http://dx.doi.org/10.1016/S0361-9230(01)00740-7] [PMID: 11849819] 
[273] 
Violet, J.M.; Downie, D.L.; Nakisa, R.C.; Lieb, W.R.; Franks, N.P. Differential sensitivities of mammalian neuronal and muscle nicotinic acetylcholine receptors to general anesthetics. Anesthesiology,  1997, 86(4), 866-874.
[http://dx.doi.org/10.1097/00000542-199704000-00017] [PMID: 9105231] 
[274] 
Cooper, E.; Couturier, S.; Ballivet, M. Pentameric structure and subunit stoichiometry of a neuronal nicotinic acetylcholine receptor. Nature,  1991, 350(6315), 235-238.
[http://dx.doi.org/10.1038/350235a0] [PMID: 2005979] 
[275] 
Role, L.W.; Berg, D.K. Nicotinic receptors in the development and modulation of CNS synapses. Neuron,  1996, 16(6), 1077-1085.
[http://dx.doi.org/10.1016/S0896-6273(00)80134-8] [PMID: 8663984] 
[276] 
McGehee, D.S.; Heath, M.J.; Gelber, S.; Devay, P.; Role, L.W. Nicotine enhancement of fast excitatory synaptic transmission in CNS by presynaptic receptors. Science,  1995, 269(5231), 1692-1696.
[http://dx.doi.org/10.1126/science.7569895] [PMID: 7569895] 
[277] 
McGehee, D.S.; Role, L.W. Physiological diversity of nicotinic acetylcholine receptors expressed by vertebrate neurons. Annu. Rev. Physiol.,  1995, 57, 521-546.
[http://dx.doi.org/10.1146/annurev.ph.57.030195.002513] [PMID: 7778876] 
[278] 
Arimura, H.; Ikemoto, Y. Action of enflurane on cholinergic transmission in identified Aplysia neurones. Br. J. Pharmacol.,  1986, 89(3), 573-582.
[http://dx.doi.org/10.1111/j.1476-5381.1986.tb11158.x] [PMID: 3026548] 
[279] 
McKenzie, D.; Franks, N.P.; Lieb, W.R. Actions of general anaesthetics on a neuronal nicotinic acetylcholine receptor in isolated identified neurones of Lymnaea stagnalis. Br. J. Pharmacol.,  1995, 115(2), 275-282.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb15874.x] [PMID: 7670729] 
[280] 
Yashima, N.; Wada, A.; Izumi, F. Halothane inhibits the cholinergic-receptor-mediated influx of calcium in primary culture of bovine adrenal medulla cells. Anesthesiology,  1986, 64(4), 466-472.
[http://dx.doi.org/10.1097/00000542-198604000-00009] [PMID: 2421612] 
[281] 
Pocock, G.; Richards, C.D. The action of volatile anaesthetics on stimulus-secretion coupling in bovine adrenal chromaffin cells. Br. J. Pharmacol.,  1988, 95(1), 209-217.
[http://dx.doi.org/10.1111/j.1476-5381.1988.tb16566.x] [PMID: 2464384] 
[282] 
Cardoso, R.A.; Yamakura, T.; Brozowski, S.J.; Chavez-Noriega, L.E.; Harris, R.A. Human neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes predict efficacy of halogenated compounds that disobey the Meyer-Overton rule. Anesthesiology,  1999, 91(5), 1370-1377.
[http://dx.doi.org/10.1097/00000542-199911000-00029] [PMID: 10551588] 
[283] 
Yamakura, T.; Chavez-Noriega, L.E.; Harris, R.A. Subunit-dependent inhibition of human neuronal nicotinic acetylcholine receptors and other ligand-gated ion channels by dissociative anesthetics ketamine and dizocilpine. Anesthesiology,  2000, 92(4), 1144-1153.
[http://dx.doi.org/10.1097/00000542-200004000-00033] [PMID: 10754635] 
[284] 
Yamashita, M.; Mori, T.; Nagata, K.; Yeh, J.Z.; Narahashi, T. Isoflurane modulation of neuronal nicotinic acetylcholine receptors expressed in human embryonic kidney cells. Anesthesiology,  2005, 102(1), 76-84.
[http://dx.doi.org/10.1097/00000542-200501000-00015] [PMID: 15618790] 
[285] 
Yamakura, T.; Borghese, C.; Harris, R.A. A transmembrane site determines sensitivity of neuronal nicotinic acetylcholine receptors to general anesthetics. J. Biol. Chem.,  2000, 275(52), 40879-40886.
[http://dx.doi.org/10.1074/jbc.M005771200] [PMID: 11020384] 
[286] 
Mowrey, D.D.; Liu, Q.; Bondarenko, V.; Chen, Q.; Seyoum, E.; Xu, Y.; Wu, J.; Tang, P. Insights into distinct modulation of α7 and α7β2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane. J. Biol. Chem.,  2013, 288(50), 35793-35800.
[http://dx.doi.org/10.1074/jbc.M113.508333] [PMID: 24194515] 
[287] 
Bondarenko, V.; Mowrey, D.D.; Tillman, T.S.; Seyoum, E.; Xu, Y.; Tang, P. NMR structures of the human α7 nAChR transmembrane domain and associated anesthetic binding sites. Biochim. Biophys. Acta,  2014, 1838(5), 1389-1395.
[http://dx.doi.org/10.1016/j.bbamem.2013.12.018] [PMID: 24384062] 
[288] 
Flood, P.; Ramirez-Latorre, J.; Role, L. Alpha 4 beta 2 neuronal nicotinic acetylcholine receptors in the central nervous system are inhibited by isoflurane and propofol, but alpha 7-type nicotinic acetylcholine receptors are unaffected. Anesthesiology,  1997, 86(4), 859-865.
[http://dx.doi.org/10.1097/00000542-199704000-00016] [PMID: 9105230] 
[289] 
Zhang, L.; Oz, M.; Stewart, R.R.; Peoples, R.W.; Weight, F.F. Volatile general anaesthetic actions on recombinant nACh alpha 7, 5-HT3 and chimeric nACh alpha 7-5-HT3 receptors expressed in Xenopus oocytes. Br. J. Pharmacol.,  1997, 120(3), 353-355.
[http://dx.doi.org/10.1038/sj.bjp.0700934] [PMID: 9031735] 
[290] 
Mori, T.; Zhao, X.; Zuo, Y.; Aistrup, G.L.; Nishikawa, K.; Marszalec, W.; Yeh, J.Z.; Narahashi, T. Modulation of neuronal nicotinic acetylcholine receptors by halothane in rat cortical neurons. Mol. Pharmacol.,  2001, 59(4), 732-743.
[http://dx.doi.org/10.1124/mol.59.4.732] [PMID: 11259617] 
[291] 
Liu, L.T.; Willenbring, D.; Xu, Y.; Tang, P. General anesthetic binding to neuronal alpha4beta2 nicotinic acetylcholine receptor and its effects on global dynamics. J. Phys. Chem. B,  2009, 113(37), 12581-12589.
[http://dx.doi.org/10.1021/jp9039513] [PMID: 19697903] 
[292] 
Eger, E.I., II; Zhang, Y.; Laster, M.; Flood, P.; Kendig, J.J.; Sonner, J.M. Acetylcholine receptors do not mediate the immobilization produced by inhaled anesthetics. Anesth. Analg.,  2002, 94(6), 1500-1504.
[PMID: 12032015] 
[293] 
Flood, P.; Sonner, J.M.; Gong, D.; Coates, K.M. Heteromeric nicotinic inhibition by isoflurane does not mediate MAC or loss of righting reflex. Anesthesiology,  2002, 97(4), 902-905.
[http://dx.doi.org/10.1097/00000542-200210000-00023] [PMID: 12357157] 
[294] 
Zhang, Y.; Laster, M.J.; Eger, E.I., II; Sharma, M.; Sonner, J.M. Blockade of acetylcholine receptors does not change the dose of etomidate required to produce immobility in rats. Anesth. Analg.,  2007, 104(4), 850-852.
[http://dx.doi.org/10.1213/01.ane.0000258018.82583.0b] [PMID: 17377093] 
[295] 
Leung, L.S.; Petropoulos, S.; Shen, B.; Luo, T.; Herrick, I.; Rajakumar, N.; Ma, J. Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics. Exp. Neurol.,  2011, 228(2), 259-269.
[http://dx.doi.org/10.1016/j.expneurol.2011.01.019] [PMID: 21295026] 
[296] 
Mori, H.; Mishina, M. Structure and function of the NMDA receptor channel. Neuropharmacology,  1995, 34(10), 1219-1237.
[http://dx.doi.org/10.1016/0028-3908(95)00109-J] [PMID: 8570021] 
[297] 
Johnson, J.W.; Ascher, P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature,  1987, 325(6104), 529-531.
[http://dx.doi.org/10.1038/325529a0] [PMID: 2433595] 
[298] 
Scheller, M.S.; Zornow, M.H.; Fleischer, J.E.; Shearman, G.T.; Greber, T.F. The noncompetitive N-methyl-D-aspartate receptor antagonist, MK-801 profoundly reduces volatile anesthetic requirements in rabbits. Neuropharmacology,  1989, 28(7), 677-681.
[http://dx.doi.org/10.1016/0028-3908(89)90150-0] [PMID: 2548110] 
[299] 
Daniell, L.C. The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics. Pharmacol. Biochem. Behav.,  1990, 36(1), 111-115.
[http://dx.doi.org/10.1016/0091-3057(90)90134-4] [PMID: 2190239] 
[300] 
Yang, J.; Zorumski, C.F. Effects of isoflurane on N-methyl-D-aspartate gated ion channels in cultured rat hippocampal neurons. Ann. N. Y. Acad. Sci.,  1991, 625, 287-289.
[http://dx.doi.org/10.1111/j.1749-6632.1991.tb33851.x] [PMID: 1711810] 
[301] 
Martin, D.C.; Abraham, J.E.; Plagenhoef, M.; Aronstam, R.S. Volatile anesthetics and NMDA receptors. Enflurane inhibition of glutamate-stimulated [3H]MK-801 binding and reversal by glycine. Neurosci. Lett.,  1991, 132(1), 73-76.
[http://dx.doi.org/10.1016/0304-3940(91)90436-W] [PMID: 1686307] 
[302] 
Martin, D.C.; Aronstam, R.S. Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain. Biochem. Pharmacol.,  1995, 50(9), 1373-1377.
[http://dx.doi.org/10.1016/0006-2952(95)02017-9] [PMID: 7503786] 
[303] 
Ishizaki, K.; Yoshida, N.; Yoon, D.M.; Yoon, M.H.; Sudoh, M.; Fujita, T. Intrathecally administered NMDA receptor antagonists reduce the MAC of isoflurane in rats. Can. J. Anaesth.,  1996, 43(7), 724-730.
[http://dx.doi.org/10.1007/BF03017958] [PMID: 8807180] 
[304] 
Ishizaki, K.; Sasaki, M.; Karasawa, S.; Obata, H.; Nara, T.; Goto, F. Intrathecal co-administration of NMDA antagonist and NK-1 antagonist reduces MAC of isoflurane in rats. Acta Anaesthesiol. Scand.,  1999, 43(7), 753-759.
[http://dx.doi.org/10.1034/j.1399-6576.1999.430711.x] [PMID: 10456816] 
[305] 
Carlà, V.; Moroni, F. General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. Neurosci. Lett.,  1992, 146(1), 21-24.
[http://dx.doi.org/10.1016/0304-3940(92)90162-Z] [PMID: 1282227] 
[306] 
Perouansky, M.; Kirson, E.D.; Yaari, Y. Mechanism of action of volatile anesthetics: effects of halothane on glutamate receptors in vitro. Toxicol. Lett.,  1998, 100-101, 65-69.
[http://dx.doi.org/10.1016/S0378-4274(98)00166-0] [PMID: 10049182] 
[307] 
MacDonald, J.F.; Bartlett, M.C.; Mody, I.; Pahapill, P.; Reynolds, J.N.; Salter, M.W.; Schneiderman, J.H.; Pennefather, P.S. Actions of ketamine, phencyclidine and MK-801 on NMDA receptor currents in cultured mouse hippocampal neurones. J. Physiol.,  1991, 432, 483-508.
[http://dx.doi.org/10.1113/jphysiol.1991.sp018396] [PMID: 1832184] 
[308] 
Mayer, M.L.; Westbrook, G.L.; Vyklický, L., Jr Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J. Neurophysiol.,  1988, 60(2), 645-663.
[http://dx.doi.org/10.1152/jn.1988.60.2.645] [PMID: 2902200] 
[309] 
Irifune, M.; Shimizu, T.; Nomoto, M.; Fukuda, T. Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor-channel complex in mice. Brain Res.,  1992, 596(1-2), 1-9.
[http://dx.doi.org/10.1016/0006-8993(92)91525-J] [PMID: 1281742] 
[310] 
Orser, B.A.; Pennefather, P.S.; MacDonald, J.F. Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors. Anesthesiology,  1997, 86(4), 903-917.
[http://dx.doi.org/10.1097/00000542-199704000-00021] [PMID: 9105235] 
[311] 
Yamakura, T.; Sakimura, K.; Shimoji, K.; Mishina, M. Effects of propofol on various AMPA-, kainate- and NMDA-selective glutamate receptor channels expressed in Xenopus oocytes. Neurosci. Lett.,  1995, 188(3), 187-190.
[http://dx.doi.org/10.1016/0304-3940(95)11431-U] [PMID: 7609905] 
[312] 
Bianchi, M.; Battistin, T.; Galzigna, L. 2,6-diisopropylphenol, a general anesthetic, inhibits glutamate action on rat synaptosomes. Neurochem. Res.,  1991, 16(4), 443-446.
[http://dx.doi.org/10.1007/BF00965564] [PMID: 1681436] 
[313] 
Orser, B.A.; Bertlik, M.; Wang, L.Y.; MacDonald, J.F. Inhibition by propofol (2,6 di-isopropylphenol) of the N-methyl-D-aspartate subtype of glutamate receptor in cultured hippocampal neurones. Br. J. Pharmacol.,  1995, 116(2), 1761-1768.
[http://dx.doi.org/10.1111/j.1476-5381.1995.tb16660.x] [PMID: 8528557] 
[314] 
Laube, B.; Kuhse, J.; Betz, H. Evidence for a tetrameric structure of recombinant NMDA receptors. J. Neurosci.,  1998, 18(8), 2954-2961.
[http://dx.doi.org/10.1523/JNEUROSCI.18-08-02954.1998] [PMID: 9526012] 
[315] 
Gan, Q.; Salussolia, C.L.; Wollmuth, L.P. Assembly of AMPA receptors: mechanisms and regulation. J. Physiol.,  2015, 593(1), 39-48.
[http://dx.doi.org/10.1113/jphysiol.2014.273755] [PMID: 25556786] 
[316] 
Hollmann, M.W.; Liu, H.T.; Hoenemann, C.W.; Liu, W.H.; Durieux, M.E. Modulation of NMDA receptor function by ketamine and magnesium. Part II: interactions with volatile anesthetics. Anesth. Analg.,  2001, 92(5), 1182-1191.
[http://dx.doi.org/10.1097/00000539-200105000-00020] [PMID: 11323344] 
[317] 
Ogata, J.; Shiraishi, M.; Namba, T.; Smothers, C.T.; Woodward, J.J.; Harris, R.A. Effects of anesthetics on mutant N-methyl-D-aspartate receptors expressed in Xenopus oocytes. J. Pharmacol. Exp. Ther.,  2006, 318(1), 434-443.
[http://dx.doi.org/10.1124/jpet.106.101691] [PMID: 16622040] 
[318] 
Solt, K.; Eger, E.I., II; Raines, D.E. Differential modulation of human N-methyl-D-aspartate receptors by structurally diverse general anesthetics. Anesth. Analg.,  2006, 102(5), 1407-1411.
[http://dx.doi.org/10.1213/01.ane.0000204252.07406.9f] [PMID: 16632818] 
[319] 
Petrenko, A.B.; Yamakura, T.; Fujiwara, N.; Askalany, A.R.; Baba, H.; Sakimura, K. Reduced sensitivity to ketamine and pentobarbital in mice lacking the N-methyl-D-aspartate receptor GluRepsilon1 subunit. Anesth. Analg.,  2004, 99(4), 1136-1140.
[http://dx.doi.org/10.1213/01.ANE.0000131729.54986.30] [PMID: 15385364] 
[320] 
Petrenko, A.B.; Yamakura, T.; Kohno, T.; Sakimura, K.; Baba, H. Reduced immobilizing properties of isoflurane and nitrous oxide in mutant mice lacking the N-methyl-D-aspartate receptor GluR(epsilon)1 subunit are caused by the secondary effects of gene knockout. Anesth. Analg.,  2010, 110(2), 461-465.
[http://dx.doi.org/10.1213/ANE.0b013e3181c76e73] [PMID: 19933527] 
[321] 
Wang, J.Q.; Liu, X.; Zhang, G.; Parelkar, N.K.; Arora, A.; Haines, M.; Fibuch, E.E.; Mao, L. Phosphorylation of glutamate receptors: a potential mechanism for the regulation of receptor function and psychostimulant action. J. Neurosci. Res.,  2006, 84(8), 1621-1629.
[http://dx.doi.org/10.1002/jnr.21050] [PMID: 16983660] 
[322] 
Tingley, W.G.; Ehlers, M.D.; Kameyama, K.; Doherty, C.; Ptak, J.B.; Riley, C.T.; Huganir, R.L. Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies. J. Biol. Chem.,  1997, 272(8), 5157-5166.
[http://dx.doi.org/10.1074/jbc.272.8.5157] [PMID: 9030583] 
[323] 
Dudman, J.T.; Eaton, M.E.; Rajadhyaksha, A.; Macías, W.; Taher, M.; Barczak, A.; Kameyama, K.; Huganir, R.; Konradi, C. Dopamine D1 receptors mediate CREB phosphorylation via phosphorylation of the NMDA receptor at Ser897-NR1. J. Neurochem.,  2003, 87(4), 922-934.
[http://dx.doi.org/10.1046/j.1471-4159.2003.02067.x] [PMID: 14622123] 
[324] 
Kingston, S.; Mao, L.; Yang, L.; Arora, A.; Fibuch, E.E.; Wang, J.Q. Propofol inhibits phosphorylation of N-methyl-D-aspartate receptor NR1 subunits in neurons. Anesthesiology,  2006, 104(4), 763-769.
[http://dx.doi.org/10.1097/00000542-200604000-00021] [PMID: 16571972] 
[325] 
Kozinn, J.; Mao, L.; Arora, A.; Yang, L.; Fibuch, E.E.; Wang, J.Q. Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol. Anesthesiology,  2006, 105(6), 1182-1191.
[http://dx.doi.org/10.1097/00000542-200612000-00018] [PMID: 17122581] 
[326] 
Haines, M.; Mao, L.M.; Yang, L.; Arora, A.; Fibuch, E.E.; Wang, J.Q. Modulation of AMPA receptor GluR1 subunit phosphorylation in neurons by the intravenous anaesthetic propofol. Br. J. Anaesth.,  2008, 100(5), 676-682.
[http://dx.doi.org/10.1093/bja/aen051] [PMID: 18344555] 
[327] 
Shi, S.H.; Hayashi, Y.; Petralia, R.S.; Zaman, S.H.; Wenthold, R.J.; Svoboda, K.; Malinow, R. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science,  1999, 284(5421), 1811-1816.
[http://dx.doi.org/10.1126/science.284.5421.1811] [PMID: 10364548] 
[328] 
Adams, J.P.; Sweatt, J.D. Molecular psychology: roles for the ERK MAP kinase cascade in memory. Annu. Rev. Pharmacol. Toxicol.,  2002, 42, 135-163.
[http://dx.doi.org/10.1146/annurev.pharmtox.42.082701.145401] [PMID: 11807168] 
[329] 
Snyder, G.L.; Galdi, S.; Hendrick, J.P.; Hemmings, H.C., Jr General anesthetics selectively modulate glutamatergic and dopaminergic signaling via site-specific phosphorylation in vivo. Neuropharmacology,  2007, 53(5), 619-630.
[http://dx.doi.org/10.1016/j.neuropharm.2007.07.008] [PMID: 17826804] 
[330] 
Hang, L.; Shao, D.; Yang, Y.; Sun, W.; Dai, T.; Zeng, Y. Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors participate in the analgesic but not hypnotic effects of emulsified halogenated anaesthetics. Basic Clin. Pharmacol. Toxicol.,  2008, 103(1), 31-35.
[http://dx.doi.org/10.1111/j.1742-7843.2008.00270.x] [PMID: 18598297] 
[331] 
Jevtovic-Todorovic, V.; Hartman, R.E.; Izumi, Y.; Benshoff, N.D.; Dikranian, K.; Zorumski, C.F.; Olney, J.W.; Wozniak, D.F. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J. Neurosci.,  2003, 23(3), 876-882.
[http://dx.doi.org/10.1523/JNEUROSCI.23-03-00876.2003] [PMID: 12574416] 
[332] 
Perouansky, M.; Pearce, R.A. How we recall (or don’t): the hippocampal memory machine and anesthetic amnesia. Can. J. Anaesth.,  2011, 58(2), 157-166.
[http://dx.doi.org/10.1007/s12630-010-9417-y] [PMID: 21170624] 
[333] 
Sanders, R.D.; Hassell, J.; Davidson, A.J.; Robertson, N.J.; Ma, D. Impact of anaesthetics and surgery on neurodevelopment: an update. Br. J. Anaesth.,  2013, 110(Suppl. 1), 53-72.
[http://dx.doi.org/10.1093/bja/aet054] 
[334] 
Blanpied, T.A.; Ehlers, M.D. Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease. Biol. Psychiatry,  2004, 55(12), 1121-1127.
[http://dx.doi.org/10.1016/j.biopsych.2003.10.006] [PMID: 15184030] 
[335] 
De Roo, M.; Klauser, P.; Briner, A.; Nikonenko, I.; Mendez, P.; Dayer, A.; Kiss, J.Z.; Muller, D.; Vutskits, L. Anesthetics rapidly promote synaptogenesis during a critical period of brain development. PLoS One,  2009, 4(9)e7043
[http://dx.doi.org/10.1371/journal.pone.0007043] [PMID: 19756154] 
[336] 
Briner, A.; De Roo, M.; Dayer, A.; Muller, D.; Habre, W.; Vutskits, L. Volatile anesthetics rapidly increase dendritic spine density in the rat medial prefrontal cortex during synaptogenesis. Anesthesiology,  2010, 112(3), 546-556.
[http://dx.doi.org/10.1097/ALN.0b013e3181cd7942] [PMID: 20124985] 
[337] 
Briner, A.; Nikonenko, I.; De Roo, M.; Dayer, A.; Muller, D.; Vutskits, L. Developmental Stage-dependent persistent impact of propofol anesthesia on dendritic spines in the rat medial prefrontal cortex. Anesthesiology,  2011, 115(2), 282-293.
[http://dx.doi.org/10.1097/ALN.0b013e318221fbbd] [PMID: 21701379] 
[338] 
Qiu, L.; Zhu, C.; Bodogan, T.; Gómez-Galán, M.; Zhang, Y.; Zhou, K.; Li, T.; Xu, G.; Blomgren, K.; Eriksson, L.I.; Vutskits, L.; Terrando, N. Acute and long-term effects of brief sevoflurane anesthesia during the early postnatal period in rats. Toxicol. Sci.,  2016, 149(1), 121-133.
[http://dx.doi.org/10.1093/toxsci/kfv219] [PMID: 26424773] 
[339] 
Hensch, T.K. Critical period regulation. Annu. Rev. Neurosci.,  2004, 27, 549-579.
[http://dx.doi.org/10.1146/annurev.neuro.27.070203.144327] [PMID: 15217343] 
[340] 
Zhang, Z.; Zhang, J.; Li, J.; Zhang, J.; Chen, L.; Li, Y.; Guo, G. Ketamine regulates phosphorylation of CRMP2 to mediate dendritic spine plasticity. J. Mol. Neurosci.,  2020, 70(3), 353-364.
[http://dx.doi.org/10.1007/s12031-019-01419-4] [PMID: 31808033] 
[341] 
Krucker, T.; Siggins, G.R.; Halpain, S. Dynamic actin filaments are required for stable long-term potentiation (LTP) in area CA1 of the hippocampus. Proc. Natl. Acad. Sci. USA,  2000, 97(12), 6856-6861.
[http://dx.doi.org/10.1073/pnas.100139797] [PMID: 10823894] 
[342] 
Lynch, G.; Rex, C.S.; Gall, C.M. LTP consolidation: substrates, explanatory power, and functional significance. Neuropharmacology,  2007, 52(1), 12-23.
[http://dx.doi.org/10.1016/j.neuropharm.2006.07.027] [PMID: 16949110] 
[343] 
Kasai, H.; Hayama, T.; Ishikawa, M.; Watanabe, S.; Yagishita, S.; Noguchi, J. Learning rules and persistence of dendritic spines. Eur. J. Neurosci.,  2010, 32(2), 241-249.
[http://dx.doi.org/10.1111/j.1460-9568.2010.07344.x] [PMID: 20646057] 
[344] 
Head, B.P.; Patel, H.H.; Niesman, I.R.; Drummond, J.C.; Roth, D.M.; Patel, P.M. Inhibition of p75 neurotrophin receptor attenuates isoflurane-mediated neuronal apoptosis in the neonatal central nervous system. Anesthesiology,  2009, 110(4), 813-825.
[http://dx.doi.org/10.1097/ALN.0b013e31819b602b] [PMID: 19293698] 
[345] 
Lemkuil, B.P.; Head, B.P.; Pearn, M.L.; Patel, H.H.; Drummond, J.C.; Patel, P.M. Isoflurane neurotoxicity is mediated by p75NTR-RhoA activation and actin depolymerization. Anesthesiology,  2011, 114(1), 49-57.
[http://dx.doi.org/10.1097/ALN.0b013e318201dcb3] [PMID: 21169791] 
[346] 
Zimering, J.H.; Dong, Y.; Fang, F.; Huang, L.; Zhang, Y.; Xie, Z. Anesthetic Sevoflurane Causes Rho-dependent filopodial shortening in mouse neurons. PLoS One,  2016, 11(7)e0159637
[http://dx.doi.org/10.1371/journal.pone.0159637] [PMID: 27441369] 
[347] 
Jiang, S.; Hao, Z.; Li, X.; Bo, L.; Zhang, R.; Wang, Y.; Duan, X.; Kang, R.; Huang, L. Ketamine destabilizes growth of dendritic spines in developing hippocampal neurons in vitro via a Rho dependent mechanism. Mol. Med. Rep.,  2018, 18(6), 5037-5043.
[http://dx.doi.org/10.3892/mmr.2018.9531] [PMID: 30280188] 
[348] 
Poo, M.M. Neurotrophins as synaptic modulators. Nat. Rev. Neurosci.,  2001, 2(1), 24-32.
[http://dx.doi.org/10.1038/35049004] [PMID: 11253356] 
[349] 
Chapleau, C.A.; Larimore, J.L.; Theibert, A.; Pozzo-Miller, L. Modulation of dendritic spine development and plasticity by BDNF and vesicular trafficking: fundamental roles in neurodevelopmental disorders associated with mental retardation and autism. J. Neurodev. Disord.,  2009, 1(3), 185-196.
[http://dx.doi.org/10.1007/s11689-009-9027-6] [PMID: 19966931] 
[350] 
Teng, H.K.; Teng, K.K.; Lee, R.; Wright, S.; Tevar, S.; Almeida, R.D.; Kermani, P.; Torkin, R.; Chen, Z.Y.; Lee, F.S.; Kraemer, R.T.; Nykjaer, A.; Hempstead, B.L. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J. Neurosci.,  2005, 25(22), 5455-5463.
[http://dx.doi.org/10.1523/JNEUROSCI.5123-04.2005] [PMID: 15930396] 
[351] 
Cowansage, K.K.; LeDoux, J.E.; Monfils, M.H. Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity. Curr. Mol. Pharmacol.,  2010, 3(1), 12-29.
[http://dx.doi.org/10.2174/1874467211003010012] [PMID: 20030625] 
[352] 
Woo, N.H.; Teng, H.K.; Siao, C.J.; Chiaruttini, C.; Pang, P.T.; Milner, T.A.; Hempstead, B.L.; Lu, B. Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat. Neurosci.,  2005, 8(8), 1069-1077.
[http://dx.doi.org/10.1038/nn1510] [PMID: 16025106] 
[353] 
Yang, J.; Siao, C.J.; Nagappan, G.; Marinic, T.; Jing, D.; McGrath, K.; Chen, Z.Y.; Mark, W.; Tessarollo, L.; Lee, F.S.; Lu, B.; Hempstead, B.L. Neuronal release of proBDNF. Nat. Neurosci.,  2009, 12(2), 113-115.
[http://dx.doi.org/10.1038/nn.2244] [PMID: 19136973] 
[354] 
Pearn, M.L.; Hu, Y.; Niesman, I.R.; Patel, H.H.; Drummond, J.C.; Roth, D.M.; Akassoglou, K.; Patel, P.M.; Head, B.P. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology,  2012, 116(2), 352-361.
[http://dx.doi.org/10.1097/ALN.0b013e318242a48c] [PMID: 22198221] 
[355] 
Lu, L.X.; Yon, J.H.; Carter, L.B.; Jevtovic-Todorovic, V. General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain. Apoptosis,  2006, 11(9), 1603-1615.
[http://dx.doi.org/10.1007/s10495-006-8762-3] [PMID: 16738805] 
[356] 
Soppet, D.; Escandon, E.; Maragos, J.; Middlemas, D.S.; Reid, S.W.; Blair, J.; Burton, L.E.; Stanton, B.R.; Kaplan, D.R.; Hunter, T.; Nikolics, K.; Parada, L.F. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell,  1991, 65(5), 895-903.
[http://dx.doi.org/10.1016/0092-8674(91)90396-G] [PMID: 1645620] 
[357] 
Mizuno, M.; Yamada, K.; He, J.; Nakajima, A.; Nabeshima, T. Involvement of BDNF receptor TrkB in spatial memory formation. Learn. Mem.,  2003, 10(2), 108-115.
[http://dx.doi.org/10.1101/lm.56003] [PMID: 12663749] 
[358] 
Yang, T. A small molecule TrkB/TrkC neurotrophin receptor coactivator
	with distinctive effects on neuronal survival and process
	outgrowth. Neuropharmacology,,  2016, 110(Pt A), 343-361.
[359] 
Vutskits, L.; Lysakowski, C.; Czarnetzki, C.; Jenny, B.; Copin, J.C.; Tramèr, M.R. Plasma concentrations of brain-derived neurotrophic factor in patients undergoing minor surgery: a randomized controlled trial. Neurochem. Res.,  2008, 33(7), 1325-1331.
[http://dx.doi.org/10.1007/s11064-007-9586-4] [PMID: 18270817] 
[360] 
Ji, M.; Dong, L.; Jia, M.; Liu, W.; Zhang, M.; Ju, L.; Yang, J.; Xie, Z.; Yang, J. Epigenetic enhancement of brain-derived neurotrophic factor signaling pathway improves cognitive impairments induced by isoflurane exposure in aged rats. Mol. Neurobiol.,  2014, 50(3), 937-944.
[http://dx.doi.org/10.1007/s12035-014-8659-z] [PMID: 24553857] 
[361] 
Citri, A.; Malenka, R.C. Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology,  2008, 33(1), 18-41.
[http://dx.doi.org/10.1038/sj.npp.1301559] [PMID: 17728696] 
[362] 
Simon, W.; Hapfelmeier, G.; Kochs, E.; Zieglgänsberger, W.; Rammes, G. Isoflurane blocks synaptic plasticity in the mouse hippocampus. Anesthesiology,  2001, 94(6), 1058-1065.
[http://dx.doi.org/10.1097/00000542-200106000-00021] [PMID: 11465598] 
[363] 
Chen, B.; Deng, X.; Wang, B.; Liu, H. Persistent neuronal apoptosis and synaptic loss induced by multiple but not single exposure of propofol contribute to long-term cognitive dysfunction in neonatal rats. J. Toxicol. Sci.,  2016, 41(5), 627-636.
[http://dx.doi.org/10.2131/jts.41.627] [PMID: 27665772] 
[364] 
Perouansky, M.; Rau, V.; Ford, T.; Oh, S.I.; Perkins, M.; Eger, E.I., II; Pearce, R.A. Slowing of the hippocampal θ rhythm correlates with anesthetic-induced amnesia. Anesthesiology,  2010, 113(6), 1299-1309.
[http://dx.doi.org/10.1097/ALN.0b013e3181f90ccc] [PMID: 21042201] 
[365] 
Peng, S.; Zhang, Y.; Li, G.J.; Zhang, D.X.; Sun, D.P.; Fang, Q. The effect of sevoflurane on the expression of M1 acetylcholine receptor in the hippocampus and cognitive function of aged rats. Mol. Cell. Biochem.,  2012, 361(1-2), 229-233.
[http://dx.doi.org/10.1007/s11010-011-1107-8] [PMID: 21997738] 
[366] 
Wei, H.; Xiong, W.; Yang, S.; Zhou, Q.; Liang, C.; Zeng, B.X.; Xu, L. Propofol facilitates the development of long-term depression (LTD) and impairs the maintenance of long-term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Neurosci. Lett.,  2002, 324(3), 181-184.
[http://dx.doi.org/10.1016/S0304-3940(02)00183-0] [PMID: 12009518] 
[367] 
Lin, D.; Zuo, Z. Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats. Neuropharmacology,  2011, 61(8), 1354-1359.
[http://dx.doi.org/10.1016/j.neuropharm.2011.08.011] [PMID: 21864548] 
[368] 
Yu, D.; Jiang, Y.; Gao, J.; Liu, B.; Chen, P. Repeated exposure to propofol potentiates neuroapoptosis and long-term behavioral deficits in neonatal rats. Neurosci. Lett.,  2013, 534, 41-46.
[http://dx.doi.org/10.1016/j.neulet.2012.12.033] [PMID: 23295901] 
[369] 
Zhu, C.; Gao, J.; Karlsson, N.; Li, Q.; Zhang, Y.; Huang, Z.; Li, H.; Kuhn, H.G.; Blomgren, K. Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents. J. Cereb. Blood Flow Metab.,  2010, 30(5), 1017-1030.
[http://dx.doi.org/10.1038/jcbfm.2009.274] [PMID: 20068576] 
[370] 
Peng, S.; Zhang, Y.; Sun, D.P.; Zhang, D.X.; Fang, Q.; Li, G.J. The effect of sevoflurane anesthesia on cognitive function and the expression of Insulin-like Growth Factor-1 in CA1 region of hippocampus in old rats. Mol. Biol. Rep.,  2011, 38(2), 1195-1199.
[http://dx.doi.org/10.1007/s11033-010-0217-9] [PMID: 20563856] 
[371] 
MacIver, M.B.; Tauck, D.L.; Kendig, J.J. General anaesthetic modification of synaptic facilitation and long-term potentiation in hippocampus. Br. J. Anaesth.,  1989, 62(3), 301-310.
[http://dx.doi.org/10.1093/bja/62.3.301] [PMID: 2539171] 
[372] 
Haseneder, R.; Kratzer, S.; von Meyer, L.; Eder, M.; Kochs, E.; Rammes, G. Isoflurane and sevoflurane dose-dependently impair hippocampal long-term potentiation. Eur. J. Pharmacol.,  2009, 623(1-3), 47-51.
[http://dx.doi.org/10.1016/j.ejphar.2009.09.022] [PMID: 19765574] 
[373] 
Guo, D.; Gan, J.; Tan, T.; Tian, X.; Wang, G.; Ng, K.T. Neonatal exposure of ketamine inhibited the induction of hippocampal long-term potentiation without impairing the spatial memory of adult rats. Cogn. Neurodynamics,  2018, 12(4), 377-383.
[http://dx.doi.org/10.1007/s11571-018-9474-4] [PMID: 30137874] 
[374] 
Stringer, J.L.; Guyenet, P.G. Elimination of long-term potentiation in the hippocampus by phencyclidine and ketamine. Brain Res.,  1983, 258(1), 159-164.
[http://dx.doi.org/10.1016/0006-8993(83)91244-1] [PMID: 24010182] 
[375] 
MacDonald, J.F.; Miljkovic, Z.; Pennefather, P. Use-dependent block of excitatory amino acid currents in cultured neurons by ketamine. J. Neurophysiol.,  1987, 58(2), 251-266.
[http://dx.doi.org/10.1152/jn.1987.58.2.251] [PMID: 2443623] 
[376] 
Wang, R.R.; Jin, J.H.; Womack, A.W.; Lyu, D.; Kokane, S.S.; Tang, N.; Zou, X.; Lin, Q.; Chen, J. Neonatal ketamine exposure causes impairment of long-term synaptic plasticity in the anterior cingulate cortex of rats. Neuroscience,  2014, 268, 309-317.
[http://dx.doi.org/10.1016/j.neuroscience.2014.03.029] [PMID: 24674848] 
[377] 
Matsuura, T.; Kamiya, Y.; Itoh, H.; Higashi, T.; Yamada, Y.; Andoh, T. Inhibitory effects of isoflurane and nonimmobilizing halogenated compounds on neuronal nicotinic acetylcholine receptors. Anesthesiology,  2002, 97(6), 1541-1549.
[http://dx.doi.org/10.1097/00000542-200212000-00029] [PMID: 12459683] 
[378] 
Rada, E.M.; Tharakan, E.C.; Flood, P. Volatile anesthetics reduce agonist affinity at nicotinic acetylcholine receptors in the brain. Anesth. Analg.,  2003, 96(1), 108-111.
[PMID: 12505934] 
[379] 
Piao, M.H.; Liu, Y.; Wang, Y.S.; Qiu, J.P.; Feng, C.S. Volatile anesthetic isoflurane inhibits LTP induction of hippocampal CA1 neurons through α4β2 nAChR subtype-mediated mechanisms. Ann. Fr. Anesth. Reanim.,  2013, 32(10), e135-e141.
[http://dx.doi.org/10.1016/j.annfar.2013.05.012] [PMID: 24011619] 
[380] 
Mawhinney, L.J.; de Rivero Vaccari, J.P.; Alonso, O.F.; Jimenez, C.A.; Furones, C.; Moreno, W.J.; Lewis, M.C.; Dietrich, W.D.; Bramlett, H.M. Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit NR2B protein expression in the aged rat brain. Brain Res.,  2012, 1431, 23-34.
[http://dx.doi.org/10.1016/j.brainres.2011.11.004] [PMID: 22137658] 
[381] 
Uchimoto, K.; Miyazaki, T.; Kamiya, Y.; Mihara, T.; Koyama, Y.; Taguri, M.; Inagawa, G.; Takahashi, T.; Goto, T. Isoflurane impairs learning and hippocampal long-term potentiation via the saturation of synaptic plasticity. Anesthesiology,  2014, 121(2), 302-310.
[http://dx.doi.org/10.1097/ALN.0000000000000269] [PMID: 24758773] 
[382] 
Yamakura, T.; Bertaccini, E.; Trudell, J.R.; Harris, R.A. Anesthetics and ion channels: molecular models and sites of action. Annu. Rev. Pharmacol. Toxicol.,  2001, 41, 23-51.
[http://dx.doi.org/10.1146/annurev.pharmtox.41.1.23] [PMID: 11264449] 
[383] 
Kato, R.; Tachibana, K.; Nishimoto, N.; Hashimoto, T.; Uchida, Y.; Ito, R.; Tsuruga, K.; Takita, K.; Morimoto, Y. Neonatal exposure to sevoflurane causes significant suppression of hippocampal long-term potentiation in postgrowth rats. Anesth. Analg.,  2013, 117(6), 1429-1435.
[http://dx.doi.org/10.1213/ANE.0b013e3182a8c709] [PMID: 24132013] 
[384] 
Nagashima, K.; Zorumski, C.F.; Izumi, Y. Propofol inhibits long-term potentiation but not long-term depression in rat hippocampal slices. Anesthesiology,  2005, 103(2), 318-326.
[http://dx.doi.org/10.1097/00000542-200508000-00015] [PMID: 16052114] 
[385] 
Wang, W.; Wang, H.; Gong, N.; Xu, T.L. Changes of K+ -Cl- cotransporter 2 (KCC2) and circuit activity in propofol-induced impairment of long-term potentiation in rat hippocampal slices. Brain Res. Bull.,  2006, 70(4-6), 444-449.
[http://dx.doi.org/10.1016/j.brainresbull.2006.07.004] [PMID: 17027780] 
[386] 
Takamatsu, I.; Sekiguchi, M.; Wada, K.; Sato, T.; Ozaki, M. Propofol-mediated impairment of CA1 long-term potentiation in mouse hippocampal slices. Neurosci. Lett.,  2005, 389(3), 129-132.
[http://dx.doi.org/10.1016/j.neulet.2005.07.043] [PMID: 16112456] 
[387] 
Zarnowska, E.D.; Rodgers, F.C.; Oh, I.; Rau, V.; Lor, C.; Laha, K.T.; Jurd, R.; Rudolph, U.; Eger, E.I.N.; Pearce, R.A. Etomidate blocks LTP and impairs learning but does not enhance tonic inhibition in mice carrying the N265M point mutation in the beta3 subunit of the GABA(A) receptor. Neuropharmacology,  2015, 93, 171-178.
[http://dx.doi.org/10.1016/j.neuropharm.2015.01.011] [PMID: 25680234] 
[388] 
Ikonomidou, C.; Bosch, F.; Miksa, M.; Bittigau, P.; Vöckler, J.; Dikranian, K.; Tenkova, T.I.; Stefovska, V.; Turski, L.; Olney, J.W. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science,  1999, 283(5398), 70-74.
[http://dx.doi.org/10.1126/science.283.5398.70] [PMID: 9872743] 
[389] 
Fredriksson, A.; Pontén, E.; Gordh, T.; Eriksson, P. Neonatal exposure to a combination of N-methyl-D-aspartate and gamma-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits. Anesthesiology,  2007, 107(3), 427-436.
[http://dx.doi.org/10.1097/01.anes.0000278892.62305.9c] [PMID: 17721245] 
[390] 
Slikker, W., Jr; Zou, X.; Hotchkiss, C.E.; Divine, R.L.; Sadovova, N.; Twaddle, N.C.; Doerge, D.R.; Scallet, A.C.; Patterson, T.A.; Hanig, J.P.; Paule, M.G.; Wang, C. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol. Sci.,  2007, 98(1), 145-158.
[http://dx.doi.org/10.1093/toxsci/kfm084] [PMID: 17426105] 
[391] 
Satomoto, M.; Satoh, Y.; Terui, K.; Miyao, H.; Takishima, K.; Ito, M.; Imaki, J. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology,  2009, 110(3), 628-637.
[http://dx.doi.org/10.1097/ALN.0b013e3181974fa2] [PMID: 19212262] 
[392] 
Zou, X.; Patterson, T.A.; Divine, R.L.; Sadovova, N.; Zhang, X.; Hanig, J.P.; Paule, M.G.; Slikker, W., Jr; Wang, C. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int. J. Dev. Neurosci.,  2009, 27(7), 727-731.
[http://dx.doi.org/10.1016/j.ijdevneu.2009.06.010] [PMID: 19580862] 
[393] 
Brambrink, A.M.; Evers, A.S.; Avidan, M.S.; Farber, N.B.; Smith, D.J.; Zhang, X.; Dissen, G.A.; Creeley, C.E.; Olney, J.W. Isoflurane-induced neuroapoptosis in the neonatal rhesus macaque brain. Anesthesiology,  2010, 112(4), 834-841.
[http://dx.doi.org/10.1097/ALN.0b013e3181d049cd] [PMID: 20234312] 
[394] 
Zou, X.; Liu, F.; Zhang, X.; Patterson, T.A.; Callicott, R.; Liu, S.; Hanig, J.P.; Paule, M.G.; Slikker, W., Jr; Wang, C. Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey. Neurotoxicol. Teratol.,  2011, 33(5), 592-597.
[http://dx.doi.org/10.1016/j.ntt.2011.06.003] [PMID: 21708249] 
[395] 
Brambrink, A.M.; Evers, A.S.; Avidan, M.S.; Farber, N.B.; Smith, D.J.; Martin, L.D.; Dissen, G.A.; Creeley, C.E.; Olney, J.W. Ketamine-induced neuroapoptosis in the fetal and neonatal rhesus macaque brain. Anesthesiology,  2012, 116(2), 372-384.
[http://dx.doi.org/10.1097/ALN.0b013e318242b2cd] [PMID: 22222480] 
[396] 
Creeley, C.; Dikranian, K.; Dissen, G.; Martin, L.; Olney, J.; Brambrink, A. Propofol-induced apoptosis of neurones and oligodendrocytes in fetal and neonatal rhesus macaque brain. Br. J. Anaesth.,  2013(1 Suppl. 1), 29-38.
[http://dx.doi.org/10.1093/bja/aet173] 
[397] 
Noguchi, K.K.; Johnson, S.A.; Dissen, G.A.; Martin, L.D.; Manzella, F.M.; Schenning, K.J.; Olney, J.W.; Brambrink, A.M. Isoflurane exposure for three hours triggers apoptotic cell death in neonatal macaque brain. Br. J. Anaesth.,  2017, 119(3), 524-531.
[http://dx.doi.org/10.1093/bja/aex123] [PMID: 28969320] 
[398] 
Paule, M.G.; Li, M.; Allen, R.R.; Liu, F.; Zou, X.; Hotchkiss, C.; Hanig, J.P.; Patterson, T.A.; Slikker, W., Jr; Wang, C. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol. Teratol.,  2011, 33(2), 220-230.
[http://dx.doi.org/10.1016/j.ntt.2011.01.001] [PMID: 21241795] 
[399] 
Neudecker, V.; Perez-Zoghbi, J.F.; Coleman, K.; Neuringer, M.; Robertson, N.; Bemis, A.; Glickman, B.; Schenning, K.J.; Fair, D.A.; Martin, L.D.; Dissen, G.A.; Brambrink, A.M. Infant isoflurane exposure affects social behaviours, but does not impair specific cognitive domains in juvenile non-human primates. Br. J. Anaesth.,  2021, 126(2), 486-499.
[http://dx.doi.org/10.1016/j.bja.2020.10.015] [PMID: 33198945] 
[400] 
Coleman, K.; Robertson, N.D.; Dissen, G.A.; Neuringer, M.D.; Martin, L.D.; Cuzon Carlson, V.C.; Kroenke, C.; Fair, D.; Brambrink, A.M. Isoflurane anesthesia has long-term consequences on motor and behavioral development in infant rhesus macaques. Anesthesiology,  2017, 126(1), 74-84.
[http://dx.doi.org/10.1097/ALN.0000000000001383] [PMID: 27749311] 
[401] 
Xiao, H.; Liu, B.; Chen, Y.; Zhang, J. Learning, memory and synaptic plasticity in hippocampus in rats exposed to sevoflurane. Int. J. Dev. Neurosci.,  2016, 48, 38-49.
[http://dx.doi.org/10.1016/j.ijdevneu.2015.11.001] [PMID: 26612208] 
[402] 
Guo, S.; Liu, L.; Wang, C.; Jiang, Q.; Dong, Y.; Tian, Y. Repeated exposure to sevoflurane impairs the learning and memory of older male rats. Life Sci.,  2018, 192, 75-83.
[http://dx.doi.org/10.1016/j.lfs.2017.11.025] [PMID: 29155302] 
[403] 
Huang, L.; Yang, G. Repeated exposure to ketamine-xylazine during early development impairs motor learning-dependent dendritic spine plasticity in adulthood. Anesthesiology,  2015, 122(4), 821-831.
[http://dx.doi.org/10.1097/ALN.0000000000000579] [PMID: 25575163] 
[404] 
Liu, J.; Zhao, Y.; Yang, J.; Zhang, X.; Zhang, W.; Wang, P. Neonatal repeated exposure to isoflurane not sevoflurane in mice reversibly impaired spatial cognition at juvenile-age. Neurochem. Res.,  2017, 42(2), 595-605.
[http://dx.doi.org/10.1007/s11064-016-2114-7] [PMID: 27882447] 
[405] 
Lee, B.H.; Chan, J.T.; Kraeva, E.; Peterson, K.; Sall, J.W. Isoflurane exposure in newborn rats induces long-term cognitive dysfunction in males but not females. Neuropharmacology,  2014, 83, 9-17.
[http://dx.doi.org/10.1016/j.neuropharm.2014.03.011] [PMID: 24704083] 
[406] 
Sasaki, R.J.M.; Hagelstein, M.; Lee, B.H.; Sall, J.W. Anesthesia-induced recognition deficit is improved in postnatally gonadectomized male rats. J. Neurosurg. Anesthesiol.,  2021, 33(3), 273-280.
[http://dx.doi.org/10.1097/ANA.0000000000000641] [PMID: 31503065] 
[407] 
Yi, X.; Cai, Y.; Li, W. Isoflurane damages the developing brain of mice and induces subsequent learning and memory deficits through FASL-FAS Signaling. BioMed Res. Int.,  2015, 2015315872
[http://dx.doi.org/10.1155/2015/315872] [PMID: 26609525] 
[408] 
Li, X.; Wei, K.; Hu, R.; Zhang, B.; Li, L.; Wan, L.; Zhang, C.; Yao, W. Upregulation of Cdh1 attenuates isoflurane-induced neuronal apoptosis and long-term cognitive impairments in developing rats. Front. Cell. Neurosci.,  2017, 11, 368.
[http://dx.doi.org/10.3389/fncel.2017.00368] [PMID: 29218001] 
[409] 
Peng, S.; Zhang, Y.; Zhang, J.; Wang, H.; Ren, B. Effect of ketamine on ERK expression in hippocampal neural cell and the ability of learning behavior in minor rats. Mol. Biol. Rep.,  2010, 37(7), 3137-3142.
[http://dx.doi.org/10.1007/s11033-009-9892-9] [PMID: 19826911] 
[410] 
Huang, L.; Liu, Y.; Jin, W.; Ji, X.; Dong, Z. Ketamine potentiates hippocampal neurodegeneration and persistent learning and memory impairment through the PKCγ-ERK signaling pathway in the developing brain. Brain Res.,  2012, 1476, 164-171.
[http://dx.doi.org/10.1016/j.brainres.2012.07.059] [PMID: 22985497] 
[411] 
Yu, X.; Liu, Y.; Bo, S.; Qinghua, L. Effects of sevoflurane on learning, memory, and expression of pERK1/2 in hippocampus in neonatal rats. Acta Anaesthesiol. Scand.,  2015, 59(1), 78-84.
[http://dx.doi.org/10.1111/aas.12433] [PMID: 25349022] 
[412] 
Liang, L.; Xie, R.; Lu, R.; Ma, R.; Wang, X.; Wang, F.; Liu, B.; Wu, S.; Wang, Y.; Zhang, H. Involvement of homodomain interacting protein kinase 2-c-Jun N-terminal kinase/c-Jun cascade in the long-term synaptic toxicity and cognition impairment induced by neonatal Sevoflurane exposure. J. Neurochem.,  2020, 154(4), 372-388.
[http://dx.doi.org/10.1111/jnc.14910] [PMID: 31705656] 
[413] 
Wang, S.Q.; Fang, F.; Xue, Z.G.; Cang, J.; Zhang, X.G. Neonatal sevoflurane anesthesia induces long-term memory impairment and decreases hippocampal PSD-95 expression without neuronal loss. Eur. Rev. Med. Pharmacol. Sci.,  2013, 17(7), 941-950.
[PMID: 23640442] 
[414] 
Ling, Y.Z.; Ma, W.; Yu, L.; Zhang, Y.; Liang, Q.S. Decreased PSD95 expression in medial prefrontal cortex (mPFC) was associated with cognitive impairment induced by sevoflurane anesthesia. J. Zhejiang Univ. Sci. B,  2015, 16(9), 763-771.
[http://dx.doi.org/10.1631/jzus.B1500006] [PMID: 26365118] 
[415] 
Schaefer, M.L.; Perez, P.J.; Wang, M.; Gray, C.; Krall, C.; Sun, X.; Hunter, E.; Skinner, J.; Johns, R.A. Neonatal isoflurane anesthesia or disruption of postsynaptic density-95 protein interactions change dendritic spine densities and cognitive function in juvenile mice. Anesthesiology,  2020, 133(4), 812-823.
[http://dx.doi.org/10.1097/ALN.0000000000003482] [PMID: 32773681] 
[416] 
Wiklund, A.; Granon, S.; Faure, P.; Sundman, E.; Changeux, J.P.; Eriksson, L.I. Object memory in young and aged mice after sevoflurane anaesthesia. Neuroreport,  2009, 20(16), 1419-1423.
[http://dx.doi.org/10.1097/WNR.0b013e328330cd2b] [PMID: 19738500] 
[417] 
Su, D.; Zhao, Y.; Wang, B.; Xu, H.; Li, W.; Chen, J.; Wang, X. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil. PLoS One,  2011, 6(11)e27632
[http://dx.doi.org/10.1371/journal.pone.0027632] [PMID: 22114680] 
[418] 
Wang, H.; Xu, Z.; Feng, C.; Wang, Y.; Jia, X.; Wu, A.; Yue, Y. Changes of learning and memory in aged rats after isoflurane inhalational anaesthesia correlated with hippocampal acetylcholine level. Ann. Fr. Anesth. Reanim.,  2012, 31(3), e61-e66.
[http://dx.doi.org/10.1016/j.annfar.2011.02.005] [PMID: 22301386] 
[419] 
Xiong, L.; Duan, L.; Xu, W.; Wang, Z. Nerve growth factor metabolic dysfunction contributes to sevoflurane-induced cholinergic degeneration and cognitive impairments. Brain Res.,  2019, 1707, 107-116.
[http://dx.doi.org/10.1016/j.brainres.2018.11.033] [PMID: 30481505] 
[420] 
Kong, F.J.; Ma, L.L.; Zhang, H.H.; Zhou, J.Q. Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats. J. Surg. Res.,  2015, 194(1), 255-261.
[http://dx.doi.org/10.1016/j.jss.2014.09.043] [PMID: 25450597] 
[421] 
Tang, X.; Li, Y.; Ao, J.; Ding, L.; Liu, Y.; Yuan, Y.; Wang, Z.; Wang, G. Role of α7nAChR-NMDAR in sevoflurane-induced memory deficits in the developing rat hippocampus. PLoS One,  2018, 13(2)e0192498
[http://dx.doi.org/10.1371/journal.pone.0192498] [PMID: 29401517] 
[422] 
Li, Z.; Ni, C.; Xia, C.; Jaw, J.; Wang, Y.; Cao, Y.; Xu, M.; Guo, X. Calcineurin/nuclear factor-κB signaling mediates isoflurane-induced hippocampal neuroinflammation and subsequent cognitive impairment in aged rats. Mol. Med. Rep.,  2017, 15(1), 201-209.
[http://dx.doi.org/10.3892/mmr.2016.5967] [PMID: 27909728] 
[423] 
Stratmann, G.; Sall, J.W.; May, L.D.; Bell, J.S.; Magnusson, K.R.; Rau, V.; Visrodia, K.H.; Alvi, R.S.; Ku, B.; Lee, M.T.; Dai, R. Isoflurane differentially affects neurogenesis and long-term neurocognitive function in 60-day-old and 7-day-old rats. Anesthesiology,  2009, 110(4), 834-848.
[http://dx.doi.org/10.1097/ALN.0b013e31819c463d] [PMID: 19293705] 
[424] 
Stratmann, G.; Sall, J.W.; Bell, J.S.; Alvi, R.S.; May, Ld.; Ku, B.; Dowlatshahi, M.; Dai, R.; Bickler, P.E.; Russell, I.; Lee, M.T.; Hrubos, M.W.; Chiu, C. Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats. Anesthesiology,  2010, 112(2), 305-315.
[http://dx.doi.org/10.1097/ALN.0b013e3181ca33a1] [PMID: 20098132] 
[425] 
Callaway, J.K.; Jones, N.C.; Royse, A.G.; Royse, C.F. Memory impairment in rats after desflurane anesthesia is age and dose dependent. J. Alzheimers Dis.,  2015, 44(3), 995-1005.
[http://dx.doi.org/10.3233/JAD-132444] [PMID: 25380590] 
[426] 
Huang, H.; Liu, C.M.; Sun, J.; Jin, W.J.; Wu, Y.Q.; Chen, J. Repeated 2% sevoflurane administration in 7 and 60-day-old rats: Neurotoxicity and neurocognitive dysfunction. Anaesthesist,  2017, 66(11), 850-857.
[http://dx.doi.org/10.1007/s00101-017-0359-4] [PMID: 28914327] 
[427] 
Liang, X.; Zhang, Y.; Zhang, C.; Tang, C.; Wang, Y.; Ren, J.; Chen, X.; Zhang, Y.; Zhu, Z. Effect of repeated neonatal sevoflurane exposure on the learning, memory and synaptic plasticity at juvenile and adult age. Am. J. Transl. Res.,  2017, 9(11), 4974-4983.
[PMID: 29218095] 
[428] 
Callaway, J.K.; Jones, N.C.; Royse, C.F. Isoflurane induces cognitive deficits in the Morris water maze task in rats. Eur. J. Anaesthesiol.,  2012, 29(5), 239-245.
[http://dx.doi.org/10.1097/EJA.0b013e32835103c1] [PMID: 22343609] 
[429] 
Martin, L.J.; Oh, G.H.; Orser, B.A. Etomidate targets alpha5 gamma-aminobutyric acid subtype A receptors to regulate synaptic plasticity and memory blockade. Anesthesiology,  2009, 111(5), 1025-1035.
[http://dx.doi.org/10.1097/ALN.0b013e3181bbc961] [PMID: 19809285] 
[430] 
Zurek, A.A.; Bridgwater, E.M.; Orser, B.A. Inhibition of α5 γ-Aminobutyric acid type A receptors restores recognition memory after general anesthesia. Anesth. Analg.,  2012, 114(4), 845-855.
[http://dx.doi.org/10.1213/ANE.0b013e31824720da] [PMID: 22383672] 
[431] 
Zurek, A.A.; Yu, J.; Wang, D.S.; Haffey, S.C.; Bridgwater, E.M.; Penna, A.; Lecker, I.; Lei, G.; Chang, T.; Salter, E.W.; Orser, B.A. Sustained increase in α5GABAA receptor function impairs memory after anesthesia. J. Clin. Invest.,  2014, 124(12), 5437-5441.
[http://dx.doi.org/10.1172/JCI76669] [PMID: 25365226] 
[432] 
Landin, J.D.; Palac, M.; Carter, J.M.; Dzumaga, Y.; Santerre-Anderson, J.L.; Fernandez, G.M.; Savage, L.M.; Varlinskaya, E.I.; Spear, L.P.; Moore, S.D.; Swartzwelder, H.S.; Fleming, R.L.; Werner, D.F. General anesthetic exposure in adolescent rats causes persistent maladaptations in cognitive and affective behaviors and neuroplasticity. Neuropharmacology,  2019, 150, 153-163.
[http://dx.doi.org/10.1016/j.neuropharm.2019.03.022] [PMID: 30926450] 
[433] 
Wu, J.; Bie, B.; Naguib, M. Epigenetic manipulation of brain-derived neurotrophic factor improves memory deficiency induced by neonatal anesthesia in rats. Anesthesiology,  2016, 124(3), 624-640.
[http://dx.doi.org/10.1097/ALN.0000000000000981] [PMID: 26649423] 
[434] 
Zhang, F.; Zhu, Z.Q.; Liu, D.X.; Zhang, C.; Gong, Q.H.; Zhu, Y.H. Emulsified isoflurane anesthesia decreases brain-derived neurotrophic factor expression and induces cognitive dysfunction in adult rats. Exp. Ther. Med.,  2014, 8(2), 471-477.
[http://dx.doi.org/10.3892/etm.2014.1769] [PMID: 25009603] 
[435] 
Xu, Z.; Qian, B. Sevoflurane anesthesia-mediated oxidative stress and cognitive impairment in hippocampal neurons of old rats can be ameliorated by expression of brain derived neurotrophic factor. Neurosci. Lett.,  2020, 721134785
[http://dx.doi.org/10.1016/j.neulet.2020.134785] [PMID: 32027953] 
[436] 
Goulart, B.K.; de Lima, M.N.; de Farias, C.B.; Reolon, G.K.; Almeida, V.R.; Quevedo, J.; Kapczinski, F.; Schröder, N.; Roesler, R. Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience,  2010, 167(4), 969-973.
[http://dx.doi.org/10.1016/j.neuroscience.2010.03.032] [PMID: 20338225] 
[437] 
Zhang, G.; Dong, Y.; Zhang, B.; Ichinose, F.; Wu, X.; Culley, D.J.; Crosby, G.; Tanzi, R.E.; Xie, Z. Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. J. Neurosci.,  2008, 28(17), 4551-4560.
[http://dx.doi.org/10.1523/JNEUROSCI.5694-07.2008] [PMID: 18434534] 
[438] 
Zhao, Y.; Liang, G.; Chen, Q.; Joseph, D.J.; Meng, Q.; Eckenhoff, R.G.; Eckenhoff, M.F.; Wei, H. Anesthetic-induced neurodegeneration mediated via inositol 1,4,5-trisphosphate receptors. J. Pharmacol. Exp. Ther.,  2010, 333(1), 14-22.
[http://dx.doi.org/10.1124/jpet.109.161562] [PMID: 20086058] 
[439] 
Wang, H.; Dong, Y.; Zhang, J.; Xu, Z.; Wang, G.; Swain, C.A.; Zhang, Y.; Xie, Z. Isoflurane induces endoplasmic reticulum stress and caspase activation through ryanodine receptors. Br. J. Anaesth.,  2014, 113(4), 695-707.
[http://dx.doi.org/10.1093/bja/aeu053] [PMID: 24699520] 
[440] 
Eckenhoff, R.G.; Johansson, J.S.; Wei, H.; Carnini, A.; Kang, B.; Wei, W.; Pidikiti, R.; Keller, J.M.; Eckenhoff, M.F. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology,  2004, 101(3), 703-709.
[http://dx.doi.org/10.1097/00000542-200409000-00019] [PMID: 15329595] 
[441] 
Xie, Z.; Dong, Y.; Maeda, U.; Alfille, P.; Culley, D.J.; Crosby, G.; Tanzi, R.E. The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels. Anesthesiology,  2006, 104(5), 988-994.
[http://dx.doi.org/10.1097/00000542-200605000-00015] [PMID: 16645451] 
[442] 
Bianchi, S.L.; Tran, T.; Liu, C.; Lin, S.; Li, Y.; Keller, J.M.; Eckenhoff, R.G.; Eckenhoff, M.F. Brain and behavior changes in 12-month-old Tg2576 and nontransgenic mice exposed to anesthetics. Neurobiol. Aging,  2008, 29(7), 1002-1010.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.02.009] [PMID: 17346857] 
[443] 
Zhang, S.; Hu, X.; Guan, W.; Luan, L.; Li, B.; Tang, Q.; Fan, H. Isoflurane anesthesia promotes cognitive impairment by inducing expression of β-amyloid protein-related factors in the hippocampus of aged rats. PLoS One,  2017, 12(4)e0175654
[http://dx.doi.org/10.1371/journal.pone.0175654] [PMID: 28403230] 
[444] 
Liu, H.; Weng, H. Up-regulation of Alzheimer’s disease-associated proteins may cause enflurane anesthesia induced cognitive decline in aged rats. Neurol. Sci.,  2014, 35(2), 185-189.
[http://dx.doi.org/10.1007/s10072-013-1474-x] [PMID: 23934553] 
[445] 
Li, C.; Liu, S.; Xing, Y.; Tao, F. The role of hippocampal tau protein phosphorylation in isoflurane-induced cognitive dysfunction in transgenic APP695 mice. Anesth. Analg.,  2014, 119(2), 413-419.
[http://dx.doi.org/10.1213/ANE.0000000000000315] [PMID: 24977637] 
[446] 
Tao, G.; Zhang, J.; Zhang, L.; Dong, Y.; Yu, B.; Crosby, G.; Culley, D.J.; Zhang, Y.; Xie, Z. Sevoflurane induces tau phosphorylation and glycogen synthase kinase 3β activation in young mice. Anesthesiology,  2014, 121(3), 510-527.
[http://dx.doi.org/10.1097/ALN.0000000000000278] [PMID: 24787352] 
[447] 
Yu, Y.; Yang, Y.; Tan, H.; Boukhali, M.; Khatri, A.; Yu, Y.; Hua, F.; Liu, L.; Li, M.; Yang, G.; Dong, Y.; Zhang, Y.; Haas, W.; Xie, Z. Tau Contributes to Sevoflurane-induced Neurocognitive Impairment in Neonatal Mice. Anesthesiology,  2020, 133(3), 595-610.
[http://dx.doi.org/10.1097/ALN.0000000000003452] [PMID: 32701572] 
[448] 
Le Freche, H.; Brouillette, J.; Fernandez-Gomez, F.J.; Patin, P.; Caillierez, R.; Zommer, N.; Sergeant, N.; Buée-Scherrer, V.; Lebuffe, G.; Blum, D.; Buée, L. Tau phosphorylation and sevoflurane anesthesia: an association to postoperative cognitive impairment. Anesthesiology,  2012, 116(4), 779-787.
[http://dx.doi.org/10.1097/ALN.0b013e31824be8c7] [PMID: 22343471] 
[449] 
Wang, L.; Zheng, M.; Wu, S.; Niu, Z. MicroRNA-188-3p is involved in sevoflurane anesthesia-induced neuroapoptosis by targeting MDM2. Mol. Med. Rep.,  2018, 17(3), 4229-4236.
[http://dx.doi.org/10.3892/mmr.2018.8437] [PMID: 29344658] 
[450] 
Evered, L.; Silbert, B.; Knopman, D.S.; Scott, D.A.; DeKosky, S.T.; Rasmussen, L.S.; Oh, E.S.; Crosby, G.; Berger, M.; Eckenhoff, R.G. Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br. J. Anaesth.,  2018, 121(5), 1005-1012.
[http://dx.doi.org/10.1016/j.bja.2017.11.087] [PMID: 30336844] 
[451] 
Demeure, M.J.; Fain, M.J. The elderly surgical patient and postoperative delirium. J. Am. Coll. Surg.,  2006, 203(5), 752-757.
[http://dx.doi.org/10.1016/j.jamcollsurg.2006.07.032] [PMID: 17084339] 
[452] 
Rasmussen, L.S. Postoperative cognitive dysfunction: incidence and prevention. Baillieres. Best Pract. Res. Clin. Anaesthesiol.,  2006, 20(2), 315-330.
[http://dx.doi.org/10.1016/j.bpa.2005.10.011] [PMID: 16850780] 
[453] 
Deiner, S.; Silverstein, J.H. Postoperative delirium and cognitive dysfunction. Br. J. Anaesth.,  2009, 103(Suppl. 1), 41-46.
[http://dx.doi.org/10.1093/bja/aep291] 
[454] 
Morimoto, Y.; Yoshimura, M.; Utada, K.; Setoyama, K.; Matsumoto, M.; Sakabe, T. Prediction of postoperative delirium after abdominal surgery in the elderly. J. Anesth.,  2009, 23(1), 51-56.
[http://dx.doi.org/10.1007/s00540-008-0688-1] [PMID: 19234823] 
[455] 
Schmitt, E.M.; Marcantonio, E.R.; Alsop, D.C.; Jones, R.N.; Rogers, S.O., Jr; Fong, T.G.; Metzger, E.; Inouye, S.K. Novel risk markers and long-term outcomes of delirium: the successful aging after elective surgery (SAGES) study design and methods. J. Am. Med. Dir. Assoc.,  2012, 13(9), 818.e1-818.e10.
[http://dx.doi.org/10.1016/j.jamda.2012.08.004] [PMID: 22999782] 
[456] 
Daiello, L.A.; Racine, A.M.; Yun Gou,  R.; Marcantonio, E.R.; Xie, Z.; Kunze, L.J.; Vlassakov, K.V.; Inouye, S.K.; Jones, R.N.; Alsop, D.; Travison, T.; Arnold, S.; Cooper, Z.; Dickerson, B.; Fong, T.; Metzger, E.; Pascual-Leone, A.; Schmitt, E.M.; Shafi, M.; Cavallari, M.; Dai, W.; Dillon, S.T.; McElhaney, J.; Guttmann, C.; Hshieh, T.; Kuchel, G.; Libermann, T.; Ngo, L.; Press, D.; Saczynski, J.; Vasunilashorn, S.; O’Connor, M.; Kimchi, E.; Strauss, J.; Wong, B.; Belkin, M.; Ayres, D.; Callery, M.; Pomposelli, F.; Wright, J.; Schermerhorn, M.; Abrantes, T.; Albuquerque, A.; Bertrand, S.; Brown, A.; Callahan, A.; D’Aquila, M.; Dowal, S.; Fox, M.; Gallagher, J.; Anna Gersten, R.; Hodara, A.; Helfand, B.; Inloes, J.; Kettell, J.; Kuczmarska, A.; Nee, J.; Nemeth, E.; Ochsner, L.; Palihnich, K.; Parisi, K.; Puelle, M.; Rastegar, S.; Vella, M.; Xu, G.; Bryan, M.; Guess, J.; Enghorn, D.; Gross, A.; Gou, Y.; Habtemariam, D.; Isaza, I.; Kosar, C.; Rockett, C.; Tommet, D.; Gruen, T.; Ross, M.; Tasker, K.; Gee, J.; Kolanowski, A.; Pisani, M.; de Rooij, S.; Rogers, S.; Studenski, S.; Stern, Y.; Whittemore, A.; Gottlieb, G.; Orav, J.; Sperling, R. Postoperative delirium and postoperative cognitive dysfunction: overlap and divergence. Anesthesiology,  2019, 131(3), 477-491.
[http://dx.doi.org/10.1097/ALN.0000000000002729] [PMID: 31166241] 
[457] 
Monk, T.G.; Weldon, B.C.; Garvan, C.W.; Dede, D.E.; van der Aa, M.T.; Heilman, K.M.; Gravenstein, J.S. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology,  2008, 108(1), 18-30.
[http://dx.doi.org/10.1097/01.anes.0000296071.19434.1e] [PMID: 18156878] 
[458] 
Berger, M.; Nadler, J.W.; Browndyke, J.; Terrando, N.; Ponnusamy, V.; Cohen, H.J.; Whitson, H.E.; Mathew, J.P. Postoperative cognitive dysfunction: minding the gaps in our knowledge of a common postoperative complication in the elderly. Anesthesiol. Clin.,  2015, 33(3), 517-550.
[http://dx.doi.org/10.1016/j.anclin.2015.05.008] [PMID: 26315636] 
[459] 
Terrando, N.; Eriksson, L.I.; Eckenhoff, R.G. Perioperative neurotoxicity in the elderly: summary of the 4th International Workshop. Anesth. Analg.,  2015, 120(3), 649-652.
[http://dx.doi.org/10.1213/ANE.0000000000000624] [PMID: 25695580] 
[460] 
Williams-Russo, P.; Sharrock, N.E.; Mattis, S.; Szatrowski, T.P.; Charlson, M.E. Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial. JAMA,  1995, 274(1), 44-50.
[http://dx.doi.org/10.1001/jama.1995.03530010058035] [PMID: 7791257] 
[461] 
Mason, S.E.; Noel-Storr, A.; Ritchie, C.W. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J. Alzheimers Dis.,  2010, 22(Suppl. 3), 67-79.
[http://dx.doi.org/10.3233/JAD-2010-101086] [PMID: 20858956] 
[462] 
Silbert, B.; Evered, L.; Scott, D.A.; McMahon, S.; Choong, P.; Ames, D.; Maruff, P.; Jamrozik, K. Preexisting cognitive impairment is associated with postoperative cognitive dysfunction after hip joint replacement surgery. Anesthesiology,  2015, 122(6), 1224-1234.
[http://dx.doi.org/10.1097/ALN.0000000000000671] [PMID: 25859906] 
[463] 
Feinkohl, I.; Winterer, G.; Spies, C.D.; Pischon, T. Cognitive reserve and the risk of postoperative cognitive dysfunction. Dtsch. Arztebl. Int.,  2017, 114(7), 110-117.
[PMID: 28302254] 
[464] 
Moller, J.T.; Cluitmans, P.; Rasmussen, L.S.; Houx, P.; Rasmussen, H.; Canet, J.; Rabbitt, P.; Jolles, J.; Larsen, K.; Hanning, C.D.; Langeron, O.; Johnson, T.; Lauven, P.M.; Kristensen, P.A.; Biedler, A.; van Beem, H.; Fraidakis, O.; Silverstein, J.H.; Beneken, J.E.; Gravenstein, J.S. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. Lancet,  1998, 351(9106), 857-861.
[http://dx.doi.org/10.1016/S0140-6736(97)07382-0] [PMID: 9525362] 
[465] 
Newman, M.F.; Grocott, H.P.; Mathew, J.P.; White, W.D.; Landolfo, K.; Reves, J.G.; Laskowitz, D.T.; Mark, D.B.; Blumenthal, J.A. Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery. Stroke,  2001, 32(12), 2874-2881.
[http://dx.doi.org/10.1161/hs1201.099803] [PMID: 11739990] 
[466] 
Rohan, D.; Buggy, D.J.; Crowley, S.; Ling, F.K.; Gallagher, H.; Regan, C.; Moriarty, D.C. Increased incidence of postoperative cognitive dysfunction 24 hr after minor surgery in the elderly. Can. J. Anaesth.,  2005, 52(2), 137-142.
[http://dx.doi.org/10.1007/BF03027718] [PMID: 15684252] 
[467] 
Rörtgen, D.; Kloos, J.; Fries, M.; Grottke, O.; Rex, S.; Rossaint, R.; Coburn, M. Comparison of early cognitive function and recovery after desflurane or sevoflurane anaesthesia in the elderly: a double-blinded randomized controlled trial. Br. J. Anaesth.,  2010, 104(2), 167-174.
[http://dx.doi.org/10.1093/bja/aep369] [PMID: 20042477] 
[468] 
Royse, C.F.; Andrews, D.T.; Newman, S.N.; Stygall, J.; Williams, Z.; Pang, J.; Royse, A.G. The influence of propofol or desflurane on postoperative cognitive dysfunction in patients undergoing coronary artery bypass surgery. Anaesthesia,  2011, 66(6), 455-464.
[http://dx.doi.org/10.1111/j.1365-2044.2011.06704.x] [PMID: 21501129] 
[469] 
Zhang, B.; Tian, M.; Zhen, Y.; Yue, Y.; Sherman, J.; Zheng, H.; Li, S.; Tanzi, R.E.; Marcantonio, E.R.; Xie, Z. The effects of isoflurane and desflurane on cognitive function in humans. Anesth. Analg.,  2012, 114(2), 410-415.
[http://dx.doi.org/10.1213/ANE.0b013e31823b2602] [PMID: 22075020] 
[470] 
Chen, G.; Zhou, Y.; Shi, Q.; Zhou, H. Comparison of early recovery and cognitive function after desflurane and sevoflurane anaesthesia in elderly patients: A meta-analysis of randomized controlled trials. J. Int. Med. Res.,  2015, 43(5), 619-628.
[http://dx.doi.org/10.1177/0300060515591064] [PMID: 26232124] 
[471] 
Tachibana, S.; Hayase, T.; Osuda, M.; Kazuma, S.; Yamakage, M. Recovery of postoperative cognitive function in elderly patients after a long duration of desflurane anesthesia: a pilot study. J. Anesth.,  2015, 29(4), 627-630.
[http://dx.doi.org/10.1007/s00540-015-1979-y] [PMID: 25638572] 
[472] 
Geng, Y.J.; Wu, Q.H.; Zhang, R.Q. Effect of propofol, sevoflurane, and isoflurane on postoperative cognitive dysfunction following laparoscopic cholecystectomy in elderly patients: A randomized controlled trial. J. Clin. Anesth.,  2017, 38, 165-171.
[http://dx.doi.org/10.1016/j.jclinane.2017.02.007] [PMID: 28372661] 
[473] 
Miller, D.; Lewis, S.R.; Pritchard, M.W.; Schofield-Robinson, O.J.; Shelton, C.L.; Alderson, P.; Smith, A.F. Intravenous versus inhalational maintenance of anaesthesia for postoperative cognitive outcomes in elderly people undergoing non-cardiac surgery. Cochrane Database Syst. Rev.,  2018, 8(8)CD012317
[http://dx.doi.org/10.1002/14651858.CD012317.pub2] [PMID: 30129968] 
[474] 
Zhang, Y.; Shan, G.J.; Zhang, Y.X.; Cao, S.J.; Zhu, S.N.; Li, H.J.; Ma, D.; Wang, D.X. Propofol compared with sevoflurane general anaesthesia is associated with decreased delayed neurocognitive recovery in older adults. Br. J. Anaesth.,  2018, 121(3), 595-604.
[http://dx.doi.org/10.1016/j.bja.2018.05.059] [PMID: 30115258] 
[475] 
Qiao, Y.; Feng, H.; Zhao, T.; Yan, H.; Zhang, H.; Zhao, X. Postoperative cognitive dysfunction after inhalational anesthesia in elderly patients undergoing major surgery: the influence of anesthetic technique, cerebral injury and systemic inflammation. BMC Anesthesiol.,  2015, 15, 154.
[http://dx.doi.org/10.1186/s12871-015-0130-9] [PMID: 26497059] 
[476] 
Zhang, Y.H.; Guo, X.H.; Zhang, Q.M.; Yan, G.T.; Wang, T.L. Serum CRP and urinary trypsin inhibitor implicate postoperative cognitive dysfunction especially in elderly patients. Int. J. Neurosci.,  2015, 125(7), 501-506.
[http://dx.doi.org/10.3109/00207454.2014.949341] [PMID: 25105909] 
[477] 
Mathew, J.P.; Podgoreanu, M.V.; Grocott, H.P.; White, W.D.; Morris, R.W.; Stafford-Smith, M.; Mackensen, G.B.; Rinder, C.S.; Blumenthal, J.A.; Schwinn, D.A.; Newman, M.F. Genetic variants in P-selectin and C-reactive protein influence susceptibility to cognitive decline after cardiac surgery. J. Am. Coll. Cardiol.,  2007, 49(19), 1934-1942.
[http://dx.doi.org/10.1016/j.jacc.2007.01.080] [PMID: 17498578] 
[478] 
Mathew, J.P.; Rinder, C.S.; Howe, J.G.; Fontes, M.; Crouch, J.; Newman, M.F.; Phillips-Bute, B.; Smith, B.R. Platelet PlA2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass. Multicenter Study of Perioperative Ischemia (McSPI) Research Group. Ann. Thorac. Surg.,  2001, 71(2), 663-666.
[http://dx.doi.org/10.1016/S0003-4975(00)02335-3] [PMID: 11235724] 
[479] 
Newman, M.F.; Croughwell, N.D.; Blumenthal, J.A.; Lowry, E.; White, W.D.; Spillane, W.; Davis, R.D., Jr; Glower, D.D.; Smith, L.R.; Mahanna, E.P. Predictors of cognitive decline after cardiac operation. Ann. Thorac. Surg.,  1995, 59(5), 1326-1330.
[http://dx.doi.org/10.1016/0003-4975(95)00076-W] [PMID: 7733762] 
[480] 
Roses, A.D. A model for susceptibility polymorphisms for complex diseases: apolipoprotein E and Alzheimer disease. Neurogenetics,  1997, 1(1), 3-11.
[http://dx.doi.org/10.1007/s100480050001] [PMID: 10735268] 
[481] 
Perry, E.; Walker, M.; Grace, J.; Perry, R. Acetylcholine in mind: a neurotransmitter correlate of consciousness? Trends Neurosci.,  1999, 22(6), 273-280.
[http://dx.doi.org/10.1016/S0166-2236(98)01361-7] [PMID: 10354606] 
[482] 
Fodale, V.; Santamaria, L.B. The inhibition of central nicotinic nAch receptors is the possible cause of prolonged cognitive impairment after anesthesia. Anesth. Analg.,  2003, 97(4), 1207.
[http://dx.doi.org/10.1213/01.ANE.0000077658.77618.C1] [PMID: 14500198] 
[483] 
Fodale, V.; Santamaria, L.B. Drugs of anesthesia, central nicotinic receptors and post-operative cognitive dysfunction. Acta Anaesthesiol. Scand.,  2003, 47(9), 1180.
[http://dx.doi.org/10.1034/j.1399-6576.2003.00226.x] [PMID: 12969118] 
[484] 
Terry, R.D.; Masliah, E.; Salmon, D.P.; Butters, N.; DeTeresa, R.; Hill, R.; Hansen, L.A.; Katzman, R. Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann. Neurol.,  1991, 30(4), 572-580.
[http://dx.doi.org/10.1002/ana.410300410] [PMID: 1789684] 
[485] 
Zhang, B.; Tian, M.; Zheng, H.; Zhen, Y.; Yue, Y.; Li, T.; Li, S.; Marcantonio, E.R.; Xie, Z. Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid Aβ and τ level. Anesthesiology,  2013, 119(1), 52-60.
[http://dx.doi.org/10.1097/ALN.0b013e31828ce55d] [PMID: 23438677] 
[486] 
Breteler, M.M.; van Duijn, C.M.; Chandra, V.; Fratiglioni, L.; Graves, A.B.; Heyman, A.; Jorm, A.F.; Kokmen, E.; Kondo, K.; Mortimer, J.A. Medical history and the risk of Alzheimer’s disease: a collaborative re-analysis of case-control studies. Int. J. Epidemiol.,  1991, 20(Suppl. 2), S36-S42.
[http://dx.doi.org/10.1093/ije/20.Supplement_2.S36] [PMID: 1833352] 
[487] 
Bohnen, N.I.; Warner, M.A.; Kokmen, E.; Beard, C.M.; Kurland, L.T. Alzheimer’s disease and cumulative exposure to anesthesia: a case-control study. J. Am. Geriatr. Soc.,  1994, 42(2), 198-201.
[http://dx.doi.org/10.1111/j.1532-5415.1994.tb04952.x] [PMID: 8126336] 
[488] 
Gasparini, M.; Vanacore, N.; Schiaffini, C.; Brusa, L.; Panella, M.; Talarico, G.; Bruno, G.; Meco, G.; Lenzi, G.L. A case-control study on Alzheimer’s disease and exposure to anesthesia. Neurol. Sci.,  2002, 23(1), 11-14.
[http://dx.doi.org/10.1007/s100720200017] [PMID: 12111615] 
[489] 
Seitz, D.P.; Reimer, C.L.; Siddiqui, N. A review of epidemiological evidence for general anesthesia as a risk factor for Alzheimer’s disease. Prog. Neuropsychopharmacol. Biol. Psychiatry,  2013, 47, 122-127.
[http://dx.doi.org/10.1016/j.pnpbp.2012.06.022] [PMID: 22771690] 
[490] 
Chen, C.W.; Lin, C.C.; Chen, K.B.; Kuo, Y.C.; Li, C.Y.; Chung, C.J. Increased risk of dementia in people with previous exposure to general anesthesia: a nationwide population-based case-control study. Alzheimers Dement.,  2014, 10(2), 196-204.
[http://dx.doi.org/10.1016/j.jalz.2013.05.1766] [PMID: 23896612] 
[491] 
Jevtovic-Todorovic, V.; Absalom, A.R.; Blomgren, K.; Brambrink, A.; Crosby, G.; Culley, D.J.; Fiskum, G.; Giffard, R.G.; Herold, K.F.; Loepke, A.W.; Ma, D.; Orser, B.A.; Planel, E.; Slikker, W., Jr; Soriano, S.G.; Stratmann, G.; Vutskits, L.; Xie, Z.; Hemmings, H.C., Jr Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br. J. Anaesth.,  2013, 111(2), 143-151.
[http://dx.doi.org/10.1093/bja/aet177] [PMID: 23722106] 
[492] 
DiMaggio, C.; Sun, L.S.; Kakavouli, A.; Byrne, M.W.; Li, G. A retrospective cohort study of the association of anesthesia and hernia repair surgery with behavioral and developmental disorders in young children. J. Neurosurg. Anesthesiol.,  2009, 21(4), 286-291.
[http://dx.doi.org/10.1097/ANA.0b013e3181a71f11] [PMID: 19955889] 
[493] 
Wilder, R.T.; Flick, R.P.; Sprung, J.; Katusic, S.K.; Barbaresi, W.J.; Mickelson, C.; Gleich, S.J.; Schroeder, D.R.; Weaver, A.L.; Warner, D.O. Early exposure to anesthesia and learning disabilities in a population-based birth cohort. Anesthesiology,  2009, 110(4), 796-804.
[http://dx.doi.org/10.1097/01.anes.0000344728.34332.5d] [PMID: 19293700] 
[494] 
Flick, R.P.; Katusic, S.K.; Colligan, R.C.; Wilder, R.T.; Voigt, R.G.; Olson, M.D.; Sprung, J.; Weaver, A.L.; Schroeder, D.R.; Warner, D.O. Cognitive and behavioral outcomes after early exposure to anesthesia and surgery. Pediatrics,  2011, 128(5), e1053-e1061.
[http://dx.doi.org/10.1542/peds.2011-0351] [PMID: 21969289] 
[495] 
DiMaggio, C.; Sun, L.S.; Ing, C.; Li, G. Pediatric anesthesia and neurodevelopmental impairments: a Bayesian meta-analysis. J. Neurosurg. Anesthesiol.,  2012, 24(4), 376-381.
[http://dx.doi.org/10.1097/ANA.0b013e31826a038d] [PMID: 23076225] 
[496] 
Ing, C.H.; DiMaggio, C.J.; Whitehouse, A.J.; Hegarty, M.K.; Sun, M.; von Ungern-Sternberg, B.S.; Davidson, A.J.; Wall, M.M.; Li, G.; Sun, L.S. Neurodevelopmental outcomes after initial childhood anesthetic exposure between ages 3 and 10 years. J. Neurosurg. Anesthesiol.,  2014, 26(4), 377-386.
[http://dx.doi.org/10.1097/ANA.0000000000000121] [PMID: 25144506] 
[497] 
Fan, C.H.; Peng, B.; Zhang, F.C. The postoperative effect of sevoflurane inhalational anesthesia on cognitive function and inflammatory response of pediatric patients. Eur. Rev. Med. Pharmacol. Sci.,  2018, 22(12), 3971-3975.
[PMID: 29949172] 
[498] 
Bartels, M.; Althoff, R.R.; Boomsma, D.I. Anesthesia and cognitive performance in children: no evidence for a causal relationship. Twin Res. Hum. Genet.,  2009, 12(3), 246-253.
[http://dx.doi.org/10.1375/twin.12.3.246] [PMID: 19456216] 
[499] 
Hansen, T.G.; Pedersen, J.K.; Henneberg, S.W.; Pedersen, D.A.; Murray, J.C.; Morton, N.S.; Christensen, K. Academic performance in adolescence after inguinal hernia repair in infancy: a nationwide cohort study. Anesthesiology,  2011, 114(5), 1076-1085.
[http://dx.doi.org/10.1097/ALN.0b013e31820e77a0] [PMID: 21368654] 
[500] 
Hansen, T.G.; Pedersen, J.K.; Henneberg, S.W.; Morton, N.S.; Christensen, K. Educational outcome in adolescence following pyloric stenosis repair before 3 months of age: a nationwide cohort study. Paediatr. Anaesth.,  2013, 23(10), 883-890.
[http://dx.doi.org/10.1111/pan.12225] [PMID: 23863116] 
[501] 
Davidson, A.J.; Disma, N.; de Graaff, J.C.; Withington, D.E.; Dorris, L.; Bell, G.; Stargatt, R.; Bellinger, D.C.; Schuster, T.; Arnup, S.J.; Hardy, P.; Hunt, R.W.; Takagi, M.J.; Giribaldi, G.; Hartmann, P.L.; Salvo, I.; Morton, N.S.; von Ungern Sternberg, B.S.; Locatelli, B.G.; Wilton, N.; Lynn, A.; Thomas, J.J.; Polaner, D.; Bagshaw, O.; Szmuk, P.; Absalom, A.R.; Frawley, G.; Berde, C.; Ormond, G.D.; Marmor, J.; McCann, M.E. Neurodevelopmental outcome at 2 years of age after general anaesthesia and awake-regional anaesthesia in infancy (GAS): an international multicentre, randomised controlled trial. Lancet,  2016, 387(10015), 239-250.
[http://dx.doi.org/10.1016/S0140-6736(15)00608-X] [PMID: 26507180] 
[502] 
McCann, M.E.; de Graaff, J.C.; Dorris, L.; Disma, N.; Withington, D.; Bell, G.; Grobler, A.; Stargatt, R.; Hunt, R.W.; Sheppard, S.J.; Marmor, J.; Giribaldi, G.; Bellinger, D.C.; Hartmann, P.L.; Hardy, P.; Frawley, G.; Izzo, F.; von Ungern Sternberg, B.S.; Lynn, A.; Wilton, N.; Mueller, M.; Polaner, D.M.; Absalom, A.R.; Szmuk, P.; Morton, N.; Berde, C.; Soriano, S.; Davidson, A.J. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial. Lancet,  2019, 393(10172), 664-677.
[http://dx.doi.org/10.1016/S0140-6736(18)32485-1] [PMID: 30782342] 
[503] 
Sun, L.S.; Li, G.; Miller, T.L.; Salorio, C.; Byrne, M.W.; Bellinger, D.C.; Ing, C.; Park, R.; Radcliffe, J.; Hays, S.R.; DiMaggio, C.J.; Cooper, T.J.; Rauh, V.; Maxwell, L.G.; Youn, A.; McGowan, F.X. Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood. JAMA,  2016, 315(21), 2312-2320.
[http://dx.doi.org/10.1001/jama.2016.6967] [PMID: 27272582] 
[504] 
Warner, D.O.; Zaccariello, M.J.; Katusic, S.K.; Schroeder, D.R.; Hanson, A.C.; Schulte, P.J.; Buenvenida, S.L.; Gleich, S.J.; Wilder, R.T.; Sprung, J.; Hu, D.; Voigt, R.G.; Paule, M.G.; Chelonis, J.J.; Flick, R.P. Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia: the mayo anesthesia safety in kids (mask) study. Anesthesiology,  2018, 129(1), 89-105.
[http://dx.doi.org/10.1097/ALN.0000000000002232] [PMID: 29672337] 
Rights & Permissions Print Cite
Article Metrics
44
2
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1570159X19666210803105232	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Effects of General Anesthetics on Synaptic Transmission and Plasticity

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
