DOI: 10.7554/elife.89532.3 ISSN: 2050-084X

Combinatorial expression of γ-protocadherins regulates synaptic connectivity in the mouse neocortex

Yi-jun Zhu, Cai-yun Deng, Liu Fan, Ya-Qian Wang, Hui Zhou, Hua-tai Xu
  • General Immunology and Microbiology
  • General Biochemistry, Genetics and Molecular Biology
  • General Medicine
  • General Neuroscience

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.

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