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

 Ankang Hu1,2 · Rui Zhao1  · Baihui Ren4  · Yang Li1  · Jiangteng Lu3,4,5 · Yilin Tai1
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 
2 School of Clinical Medicine, Fudan University, Shanghai 200032, China 
3 Center for Brain Science of Shanghai Children’s Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China 
4 Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 
5 Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Shanghai 201210, China


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.

Axon initial segment; Pyramidal neurons; Heterogeneity; Chandelier cell