Division of Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
Neuron. 2013 Jun 5;78(5):839-54. doi: 10.1016/j.neuron.2013.03.031. Epub 2013 May 16.
Highly topographic organization of neural circuits exists for the regulation of various brain functions in corticobasal ganglia circuits. Although neural circuit-specific refinement during synapse development is essential for the execution of particular neural functions, the molecular and cellular mechanisms for synapse refinement are largely unknown. Here, we show that protocadherin 17 (PCDH17), one of the nonclustered δ2-protocadherin family members, is enriched along corticobasal ganglia synapses in a zone-specific manner during synaptogenesis and regulates presynaptic assembly in these synapses. PCDH17 deficiency in mice causes facilitated presynaptic vesicle accumulation and enhanced synaptic transmission efficacy in corticobasal ganglia circuits. Furthermore, PCDH17(-/-) mice exhibit antidepressant-like phenotypes that are known to be regulated by corticobasal ganglia circuits. Our findings demonstrate a critical role for PCDH17 in the synaptic development of specific corticobasal ganglia circuits and suggest the involvement of PCDH17 in such circuits in depressive behaviors.
高度的地形组织的神经网络调节各种脑功能在皮质基底节回路。虽然神经电路特定细化在突触发育是必不可少的执行特定的神经功能,分子和细胞机制的突触细化在很大程度上是未知的。在这里,我们表明原钙黏蛋白 17(PCDH17),一个非聚类δ 2-原钙黏蛋白家族成员,富集沿着皮质基底节突触在特定区域的方式在突触发生和调节突触前装配在这些突触。PCDH17 缺乏在小鼠引起促进突触前囊泡积累和增强突触传递效能在皮质基底节回路。此外,PCDH17(-/-)小鼠表现出抗抑郁样表型,这是已知的受皮质基底节回路调控。我们的研究结果表明PCDH17 在突触发育的特定皮质基底节回路的关键作用,并表明PCDH17 在这种电路中在抑郁行为的参与。
