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Science DOI:10.1126/science.1232380

Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors.

Publication TypeJournal Article
Year of Publication2013
AuthorsBurguière, E, Monteiro, P, Feng, G, Graybiel, AM
Date Published2013 Jun 07
KeywordsAnimals, Compulsive Behavior, Corpus Striatum, Disease Models, Animal, Frontal Lobe, Gene Deletion, Gene Targeting, Grooming, Male, Mice, Nerve Tissue Proteins, Neurons, Optogenetics

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.


Alternate JournalScience
PubMed ID23744950
PubMed Central IDPMC3876800
Grant ListR01 HD028341 / HD / NICHD NIH HHS / United States
R01 MH081201 / MH / NIMH NIH HHS / United States
R01 MH097104 / MH / NIMH NIH HHS / United States
R37 HD028341 / HD / NICHD NIH HHS / United States