Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors
Author(s)
Burguiere, Eric; Monteiro, Patricia; Feng, Guoping; Graybiel, Ann M.
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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.
Date issued
2013-06Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; McGovern Institute for Brain Research at MITJournal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Burguiere, E., P. Monteiro, G. Feng, and A. M. Graybiel. “Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors.” Science 340, no. 6137 (June 6, 2013): 1243–1246.
Version: Author's final manuscript
ISSN
0036-8075
1095-9203