title: Repeated cortico-striatal stimulation generates persistent OCD-like behavior.
abstract: Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sea2103@columbia.edu
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ahmari
authors.forename: Timothy
authors.initials: T
authors.lastname: Spellman
authors.forename: Neria L
authors.initials: NL
authors.lastname: Douglass
authors.forename: Mazen A
authors.initials: MA
authors.lastname: Kheirbek
authors.forename: H Blair
authors.initials: HB
authors.lastname: Simpson
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Gordon
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000256:Adenoviridae; D000818:Animals; D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000235:genetics; D001522:Behavior, Animal; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology*; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology*; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology* / Q000523:psychology*; D062308:Optogenetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D005473:Fluoxetine; D008164:Luminescent Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C054562:yellow fluorescent protein, Bacteria