Cholinergic regulation of dendritic Ca2+ spikes controls firing mode of hippocampal CA3 pyramidal neurons

Proc Natl Acad Sci U S A. 2024 Nov 12;121(46):e2321501121. doi: 10.1073/pnas.2321501121. Epub 2024 Nov 6.

Abstract

Active dendritic integrative mechanisms such as regenerative dendritic spikes enrich the information processing abilities of neurons and fundamentally contribute to behaviorally relevant computations. Dendritic Ca2+ spikes are generally thought to produce plateau-like dendritic depolarization and somatic complex spike burst (CSB) firing, which can initiate rapid changes in spatial coding properties of hippocampal pyramidal cells (PCs). However, here we reveal that a morpho-topographically distinguishable subpopulation of rat and mouse hippocampal CA3PCs exhibits compound apical dendritic Ca2+ spikes with unusually short duration that do not support the firing of sustained CSBs. These Ca2+ spikes are mediated by L-type Ca2+ channels and their time course is restricted by A- and M-type K+ channels. Cholinergic activation powerfully converts short Ca2+ spikes to long-duration forms, and facilitates and prolongs CSB firing. We propose that cholinergic neuromodulation controls the ability of a CA3PC subtype to generate sustained plateau potentials, providing a state-dependent dendritic mechanism for memory encoding and retrieval.

Keywords: CA3 pyramidal neurons; cholinergic regulation; dendritic Ca2+ spike; hippocampus.

MeSH terms

  • Action Potentials* / drug effects
  • Action Potentials* / physiology
  • Animals
  • CA3 Region, Hippocampal* / cytology
  • CA3 Region, Hippocampal* / metabolism
  • CA3 Region, Hippocampal* / physiology
  • Calcium* / metabolism
  • Dendrites* / metabolism
  • Dendrites* / physiology
  • Male
  • Mice
  • Pyramidal Cells* / metabolism
  • Pyramidal Cells* / physiology
  • Rats

Substances

  • Calcium