Obsessive-compulsive disorder (OCD) is an anxiety spectrum disorder that affects both cognition and motor behavior. Symptoms include recurrent, persistent worries (obsessions) and ritualistic, stereotyped actions (compulsions) performed to alleviate the anxiety associated with these worries. A large fraction of OCD patients do not respond to currently available treatments, highlighting the need for more basic research into the neural circuits and mechanisms underlying the disorder. Human neuroimaging studies in OCD patients have consistently shown abnormal activity in the frontal cortex and striatum, which are interconnected brain structures implicated in motor control, action selection, and habit formation. Imbalance in striatal motor control pathways is thought to underlie the aberrant repetitive behaviors characteristic of OCD. However, nothing is known about how frontal cortical areas interact with the striatum to contribute to OCD pathology, and how different downstream striatal pathways are affected. The goal of this research is to disentangle the role of specific circuit elements within the fronto-striatal network using optogenetic and pharmacogenetic tools to precisely control the activity of genetically specified cell types. [These tools can be independently targeted to fronto-striatal projection neurons as well as to different populations of downstream striatal neurons. Using well- validated rodent assays for anxiety and compulsive behavior, we will systematically optically control each circuit element in awake behaving animals to identify which cell types causally contribute to OCD-like behaviors. Ex vivo and in vivo electrophysiological techniques will then be used to track the precise cellular and synaptic changes that are associated with the stimulation-induced behavioral change.] This work will suggest targets for development of more specific and effective treatments for OCD.

Public Health Relevance

Obsessive-compulsive disorder (OCD) is a common psychiatric disease that causes debilitating anxiety as well as repetitive, ritualistic behaviors tat are uncontrollable and interfere with everyday life. Despite its prevalence, very little is known about the causes of OCD and which brain regions are involved. This research will use cutting edge brain stimulation technology to further our understanding of the neural circuits underlying OCD, and identify new and more specific ways in which to treat this disorder.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Desmond, Nancy L
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J. David Gladstone Institutes
San Francisco
United States
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