A great deal of evidence suggests that the striatum plays a central role in the manifestation of OCD.  In addition to displaying abnormal activity levels itself, it also receives direct inputs from cortical regions (such as the orbitofrontal and anterior cingulate cortices) that are abnormally active in OCD patients.  A major project in our lab is to understand a) how the physiology and activity of striatal neurons is altered in mouse models of OCD, b) how striatal neurons receive and integrate synaptic inputs from discrete brain regions, and how these innervation patterns are altered in OCD models and c) how striatal neurons plastically alter the strength of unique synaptic inputs, and how this ability is altered in OCD models.


We use a number of approaches to address these questions.  Because nearly all glutamatergic inputs to striatal projection neurons occur on dendrites, we probe dendritic excitability in normal and disease states using a combination of 2 photon laser scanning microscopy, 2 photon calcium imaging and electrophysiology.  We combine these techniques with 2 photon glutamate uncaging and stereotaxically delivered optogenetic constructs to study the synaptic physiology of defined glutamatergic afferents, and how this is altered in disease states.  We will use pharmacogenetic techniques to determine how specific circuit pathologies lead to behavioral abnormalities.