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

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.