Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China
Cai-yun Deng
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
Liu Fan
Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China
Ya-Qian Wang
Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China
Hui Zhou
Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China
Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China; Lingang Laboratory, Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai, China
In the process of synaptic formation, neurons must not only adhere to specific principles when selecting synaptic partners but also possess mechanisms to avoid undesirable connections. Yet, the strategies employed to prevent unwarranted associations have remained largely unknown. In our study, we have identified the pivotal role of combinatorial clustered protocadherin gamma (γ-PCDH) expression in orchestrating synaptic connectivity in the mouse neocortex. Through 5' end single-cell sequencing, we unveiled the intricate combinatorial expression patterns of γ-PCDH variable isoforms within neocortical neurons. Furthermore, our whole-cell patch-clamp recordings demonstrated that as the similarity in this combinatorial pattern among neurons increased, their synaptic connectivity decreased. Our findings elucidate a sophisticated molecular mechanism governing the construction of neural networks in the mouse neocortex.
