OPTOGENETIC INVESTIGATION OF CIRCUITS UNDERLYING AFFECTIVE BEHAVIOR

There is considerable evidence for circuit dysfunction anxiety disorders, but our basic knowledge of the complex neural pathways that underlie emotional behavior remains incomplete. A more complete understanding of these systems promises both to facilitate a fuller understanding of anxiety disorder pathogenesis as well as suggest novel therapeutic strategies for unmet psychiatric needs. Classically, researchers have used correlational imaging techniques, gross lesion or electrical stimulation to delineated the brain structures involved in generating affective responses. While these studies have provided a wealth of information describing the structures involved in the generation of emotional behavior, in many instances they lack sufficient regional or temporal specificity. This chapter will review recent studies using optogenetic methodologies for delineating the circuits that underlie emotional behavior. First, I will review the suite of available tools for optical inhibition and excitation, and their utility for modulating activity in a cell-type and projection-specific manner. Then, I will highlight recent experiments using these tools to dissect the circuitry that underlies emotional behavior. As anxiety disorders are increasingly being viewed as a circuit-based dysfunction, optogenetics proves to be a powerful method for identifying the circuits that generate emotional responses, and will provide essential insight for development of novel therapies.

Keywords: designer receptors exclusively activated by designer drugs (DREADD), channelrhodopsin-2 (ChR2), eNHpR, Arch, basolateral amygdala (BLA), prefrontal cortex (PFC), step-function opsin (SFO), G-protein-coupled receptor (GPCR), Elevated Plus Maze (EPM), Open Field Test (OFT)