title: Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors.
abstract: Dysfunctions in frontostriatal brain circuits have been implicated in neuropsychiatric disorders, including those characterized by the presence of repetitive behaviors. We developed an optogenetic approach to block repetitive, compulsive behavior in a mouse model in which deletion of the synaptic scaffolding gene, Sapap3, results in excessive grooming. With a delay-conditioning task, we identified in the mutants a selective deficit in behavioral response inhibition and found this to be associated with defective down-regulation of striatal projection neuron activity. Focused optogenetic stimulation of the lateral orbitofrontal cortex and its terminals in the striatum restored the behavioral response inhibition, restored the defective down-regulation, and compensated for impaired fast-spiking neuron striatal microcircuits. These findings raise promising potential for the design of targeted therapy for disorders involving excessive repetitive behavior.
authors.affiliation: McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Burguière
authors.forename: Patrícia
authors.initials: P
authors.lastname: Monteiro
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.forename: Ann M
authors.initials: AM
authors.lastname: Graybiel
mesh_terms: D000818:Animals; D003192:Compulsive Behavior / Q000628:therapy*; D003342:Corpus Striatum / Q000503:physiopathology*; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000503:physiopathology*; D017353:Gene Deletion; D018390:Gene Targeting; D006120:Grooming; D008297:Male; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000502:physiology; D062308:Optogenetics / Q000379:methods*
chemical_list: D009419:Nerve Tissue Proteins; C523020:Sapap3 protein, mouse