Su Xin, Chen Jing-Jing, Liu Lin-Yun, Huang Qian, Zhang Li-Zhao, Li Xiao-Yang, He Xiang-Nan, Lu Wenlian, Sun Shan, Li Huawei, Yu Yong-Chun
Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
Centre for Computational Systems Biology and the School of Mathematical Sciences, Fudan University, Shanghai 200433, China.
Proc Natl Acad Sci U S A. 2017 Mar 21;114(12):3228-3233. doi: 10.1073/pnas.1613237114. Epub 2017 Mar 6.
Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion of () in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover, -conditional knockout (-cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion of , decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore, -cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.
新皮层中兴奋性神经元之间的电耦合受到发育调控。它最初很显著，但在后期化学突触出现的发育阶段被消除。然而，早期电耦合网络是否广泛地对新皮层回路形成和动物行为有贡献，在很大程度上仍不清楚。在此，我们报告新生小鼠新皮层兴奋性神经元之间的电耦合对于神经元的正常发育、突触形成和动物行为至关重要。在出生前后有条件地删除小鼠新皮层表层兴奋性神经元中的（此处原文缺失具体基因名称），会显著降低出生后第5 - 6天的自发放电活动以及自发网络振荡的频率和幅度。此外，与野生型神经元相比，（此处原文缺失具体基因名称）条件性敲除（-cKO）神经元往往具有更简单的树突分支和更低的棘密度。重要的是，出生后早期而非晚期删除（此处原文缺失具体基因名称），会降低幼年和成年小鼠中微小兴奋性突触后电流（mEPSCs）的频率，而微小抑制性突触后电流（mIPSCs）不受影响。此外，（此处原文缺失具体基因名称）-cKO小鼠表现出与焦虑相关的行为增加。这些结果表明，出生后早期兴奋性神经元之间的电耦合是新皮层发育和功能的关键步骤。
