2013年9月17日火曜日

Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors

Eric Burguière, Patrícia Monteiro, Guoping Feng, Ann M. Graybiel
Science 7 June 2013: Vol. 340 no. 6137 pp. 1243-1246

マウス・オプトジェネティクス(光遺伝学)。
外側眼窩前頭皮質と線条体の経路は「強迫神経症的/衝動的な行動の抑制」に重要な役割を果たしている。

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.

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