Excitatory synapses onto axonic spines jump-start action potentials and route information flow

  • Nat Neurosci. 2026 Jun;29(6):1303-1312. doi: 10.1038/s41593-026-02282-4.
Hongkun Yang  1 ,  Kun Wang  1 ,  Yijie Chen  2 ,  Wei Ke  1 ,  Liang Li  1 ,  Yilin Tai  1  3 ,  Shuyang Wang  4 ,  Yu Kong  5 ,  Xu Wang  5 ,  Wenxin Zhang  1 ,  Bo Li  1 ,  Yong Zhang  6 ,  Miao He  1  3 ,  Chao Tan  1 ,  Jintai Yu  1 ,  Jian Wang  1 ,  Yousheng Shu  7
Affiliations
  • 1. Department of Neurology, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China.
  • 2. School of Life Sciences, Nanjing University, Nanjing, China.
  • 3. Institutes of Brain Science, Fudan University, Shanghai, China.
  • 4. Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 5. Center for Excellence in Brain Science and Technology (Institute of Neuroscience), Chinese Academy of Science, Shanghai, China.
  • 6. Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China.
  • 7. Department of Neurology, Huashan Hospital, Institute for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, MOE Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, China. [email protected].
PMID: 42141306 DOI: 10.1038/s41593-026-02282-4
Abstract

Synaptic inputs onto the dendrites and cell body integrate and trigger action potentials (APs) at the axon initial segment (AIS). The AIS receives GABAergic synaptic inputs; however, the structure and function of glutamatergic synapses at the AIS remain poorly understood. Here, we show that, in adult mice, the AIS exhibits axonic spines in about half of the neurons examined in three brain regions: the dorsal lateral septum (dLS), bed nucleus of the stria terminalis and striatum. In the dLS, axonic spines express ionotropic glutamate receptors and undergo structural plasticity. Voltage-gated Na+ channels at the AIS boost the synaptic responses of axonic spines and thus AP generation. Although hippocampal dorsal CA3 neurons synapse onto both axonic spine neurons (ASNs) and non-ASNs, they preferentially activate ASNs and subsequently inhibit non-ASNs through feedforward inhibition. Together, these results indicate that axonic spines jump-start APs in dLS neurons and route information flow from the hippocampus to downstream brain regions.

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