Protocadherin 17 Regulates Presynaptic Assembly in Topographic Corticobasal Ganglia Circuits
Protocadherin 17 Regulates Presynaptic Assembly in Topographic Corticobasal Ganglia Circuits
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DOI：
10.1016/j.neuron.2013.03.031
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发表时间：
2013-06-05
期刊：
影响因子：
16.2
通讯作者：
Yamamoto, Tadashi
中科院分区：
文献类型：
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作者：
Hoshina, Naosuke;Tanimura, Asami;Yamamoto, Tadashi
在皮质基底神经节回路中存在着高度地形化的神经回路组织，以调节各种脑功能。虽然突触发育过程中神经回路特异性的细化对于特定神经功能的执行是必不可少的，但突触细化的分子和细胞机制在很大程度上是未知的。在这里，我们发现原钙粘蛋白17 （PCDH17）是非聚集型δ 2原钙粘蛋白家族成员之一，在突触发生过程中以特定区域的方式沿皮质基底神经节突触富集，并调节这些突触的突触前组装。小鼠PCDH17缺乏导致皮质基底神经节回路突触前囊泡积聚加快，突触传递效率增强。此外，PCDH17（-/-）小鼠表现出抗抑郁样表型，这是由皮质基底神经节回路调节的。我们的研究结果表明，PCDH17在特定皮质基底神经节回路的突触发育中起关键作用，并提示PCDH17参与抑郁行为的这种回路。
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 delta 2-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.