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Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex

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Abstract

The axon initial segment (AIS) is a highly specialized axonal compartment where the action potential is initiated. The heterogeneity of AISs has been suggested to occur between interneurons and pyramidal neurons (PyNs), which likely contributes to their unique spiking properties. However, whether the various characteristics of AISs can be linked to specific PyN subtypes remains unknown. Here, we report that in the prelimbic cortex (PL) of the mouse, two types of PyNs with axon projections either to the contralateral PL or to the ipsilateral basal lateral amygdala, possess distinct AIS properties reflected by morphology, ion channel expression, action potential initiation, and axo-axonic synaptic inputs from chandelier cells. Furthermore, projection-specific AIS diversity is more prominent in the superficial layer than in the deep layer. Thus, our study reveals the cortical layer- and axon projection-specific heterogeneity of PyN AISs, which may endow the spiking of various PyN types with exquisite modulation.

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Acknowledgements

We thank Professor Zuoshi J. Huang for providing the Unc5b-CreER and Nkx2.1-Flp mice. We thank Dr. You-Sheng Shu and Dr. Miao He for their discussions and technical assistance. This work was supported by the National Natural Science Foundation of China (82071450, 31972903, and 32000681), Shanghai Pujiang Program (20PJ1401000), the Natural Science Foundation of Shanghai (20ZR1405700), Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX01), ZJ Lab, the Shanghai Center for Brain Science and Brain-Inspired Technology, and the Fudan Undergraduate Research Opportunities Program (Wangdao 20046).

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Authors and Affiliations

  1. The State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, and the Institutes of Brain Science, Fudan University, Shanghai, 200032, China

    Ankang Hu, Rui Zhao, Yang Li & Yilin Tai

  2. School of Clinical Medicine, Fudan University, Shanghai, 200032, China

    Ankang Hu

  3. Center for Brain Science of Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China

    Jiangteng Lu

  4. Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Baihui Ren & Jiangteng Lu

  5. Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai, 201210, China

    Jiangteng Lu

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Correspondence to Yang Li, Jiangteng Lu or Yilin Tai.

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Hu, A., Zhao, R., Ren, B. et al. Projection-Specific Heterogeneity of the Axon Initial Segment of Pyramidal Neurons in the Prelimbic Cortex. Neurosci. Bull. 39, 1050–1068 (2023). https://doi.org/10.1007/s12264-023-01038-5

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