Work

Optogenetic Stimulation of Lateral Orbitofronto-Striatal Pathway Suppresses Compulsive Behaviors

Year: 2013

Type: article

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.

Source: Science

DOI: 10.1126/science.1232380

Authors: Eric Burguière, Patrícia Monteiro, Guoping Feng, Ann M. Graybiel

Institutions: McGovern Institute for Brain Research, Massachusetts Institute of Technology

Language: English

Topic: Obsessive-Compulsive Spectrum Disorders

Subfield: Clinical Psychology

Field: Psychology

Domain: Social Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institute of Mental Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development