Publication Date:
2013-06-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876800/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876800/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Burguiere, Eric -- Monteiro, Patricia -- Feng, Guoping -- Graybiel, Ann M -- R01 HD028341/HD/NICHD NIH HHS/ -- R01 MH081201/MH/NIMH NIH HHS/ -- R01 MH097104/MH/NIMH NIH HHS/ -- R37 HD028341/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2013 Jun 7;340(6137):1243-6. doi: 10.1126/science.1232380.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23744950" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Compulsive Behavior/*therapy
;
Corpus Striatum/*physiopathology
;
Disease Models, Animal
;
Frontal Lobe/*physiopathology
;
Gene Deletion
;
Gene Targeting
;
Grooming
;
Male
;
Mice
;
Nerve Tissue Proteins/*genetics
;
Neurons/physiology
;
Optogenetics/*methods
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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