Talk Title: Identifying molecular and circuit changes underlying OCD-like behaviors
Compulsive behaviors are a central component of Obsessive Compulsive Disorder (OCD), as well as prominent, disabling, and notoriously-treatment resistant symptoms of many severe psychiatric disorders, including autism, schizophrenia, and addiction. Although OCD symptoms have been broadly linked to abnormal activity in cortical-basal ganglia circuits via human imaging studies, we still have a quite limited understanding of how maladaptive repetitive behaviors are encoded in the brain. Our lab is using novel technologic approaches and statistical strategies that finally allow us to address this topic by determining: 1) which neural circuits underlie maladaptive repetitive behaviors, 2) how these behaviors are encoded in the brain, and 3) when the neural code changes as these behaviors develop and resolve.
Our previous work has demonstrated that a) brief but repeated optogenetic hyperstimulation of projections from orbitofrontal cortex (OFC) to ventromedial striatum (VMS) leads to long-lasting perseverative grooming, a mouse behavior linked to OCD (Ahmari et al, Science, 2013); and b) compulsive grooming behavior is associated with increased neural activity in the striatum (measured in awake-behaving mice using both in vivo microscopy and in vivo electrophysiology). Using transgenic OCD mouse-models and healthy control mice combined with in vivo optogenetics, electrophysiology, and microscopy, we are now identifying the specific activity patterns, cell-types, and circuits responsible for the development of abnormal repetitive and compulsive behaviors. I will discuss both these ongoing mechanistic studies in mice, as well as our interdisciplinary efforts to ground our basic neuroscience experiments in findings from clinical studies.
Funding Acknowledgement: Burroughs Wellcome CAMS Award; NIMH BRAINS R01MH104255; McKnight Scholar Award; Klingenstein-Simon Fellowship; MQ Fellows Award; NIMH K08MH087718; NARSAD Young Investigator Award