Optogenetic Strategies for the Treatment of Neuropsychiatric Disorders: Circuit-Function Analysis and Clinical Implications

Abstract

The manifestation and expression of the debilitating symptoms of neuropsychiatric illnesses is in part mediated by maladaptive functional alterations in neurocircuits. Although the gross anatomical brain structures that are critical for both adaptive and maladaptive behavioral states have been described in detail, little is known about the functional connectivity between genetically distinct populations of neurons and their contribution to circuit function and behavior, mainly owing to a limitation of techniques that allow precise stimulation or inhibition of neural circuit elements in vivo. To circumvent this limitation, optogenetic strategies continue to be further refined and employed to selectively manipulate the activity of genetically distinct neuronal populations with light. In this chapter we review different basic research strategies for optogenetic experimentation and highlight their use to further delineate neural circuit function in complex neuropsychiatric models for reward dysfunction and anxiety-related disorders. In addition, we discuss translational implications of optogenetic approaches and compare these with issues often considered with traditional deep brain stimulation techniques. The reviewed data and perspective illustrate the impact and promise that optogenetic tools hold for the understanding and treatment of neuropsychiatric illnesses.