光遗传刺激外侧眶额纹状体通路可抑制强迫行为。
Optogenetic stimulation of lateral orbitofronto-striatal pathway suppresses compulsive behaviors.
机构信息
McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
出版信息
Science. 2013 Jun 7;340(6137):1243-6. doi: 10.1126/science.1232380.
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.
摘要
额眶皮质-纹状体脑回路功能障碍与神经精神疾病有关，包括以重复行为为特征的疾病。我们开发了一种光遗传学方法来阻断一种小鼠模型中的重复强迫行为，该模型中突触支架基因 Sapap3 的缺失导致过度梳理。通过延迟条件任务，我们在突变体中发现了行为反应抑制的选择性缺陷，并发现这与纹状体投射神经元活性的下调缺陷有关。外侧眶额皮质及其纹状体末端的靶向光遗传学刺激恢复了行为反应抑制，恢复了下调缺陷，并补偿了快棘神经元纹状体微电路的损伤。这些发现为设计针对涉及过度重复行为的疾病的靶向治疗提供了有希望的潜力。
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本文引用的文献
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Circuit-selective striatal synaptic dysfunction in the Sapap3 knockout mouse model of obsessive-compulsive disorder.在强迫症的Sapap3基因敲除小鼠模型中，纹状体回路选择性突触功能障碍。
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