Diversity and cholinergic regulation of dendritic Ca2+ spikes in hippocampal CA3 pyramidal neurons
Kis Noémi
János Szentágothai Neurosciences
Dr. Bereczki Dániel
HUN-REN Kísérleti Orvostudományi Kutatóintézet, tanterem
2026-03-12 10:00:00
Functional neurosciences
Dr. Sperlágh Beáta
Dr. Makara Judit
Dr. Czirják Gábor
Dr. Szűcs Attila
Dr. Hrabovszky Erik
Dr. Dávid Csaba
Dr. Holderith Noémi
Hippocampal CA3PCs play a crucial role in memory encoding and retrieval. These neurons are known to exhibit prominent CSB firing activity, which has been proposed to serve as an important signal for robust intercellular communication and synaptic plasticity. However, the mechanisms underlying CSB generation in CA3PCs remain poorly understood.
To explore the generation mechanisms of CSBs and the properties of Ca2+ spikes, we performed somatic and dendritic patch-clamp recordings combined with two-photon Ca2+ imaging in acute hippocampal slices from male rats and mice. These techniques enabled detailed characterization of dendritic Ca2+ spikes and their influence on neuronal output. Pharmacological manipulations were used to dissect the roles of different subtypes of Ca2+ and K+ channels in regulating Ca2+ spike generation. Additionally, pharmacological and optogenetic stimulation of cholinergic activity was employed to investigate neuromodulatory control over CSB activity.
Our findings reveal that CSBs in CA3PCs are driven by dendritic Ca2+ spikes, which exhibit remarkable heterogeneity across cells influenced by their topographic position and dendritic morphology. All spike forms were dominantly mediated by L-type Ca2+ channels. With dendritic recordings, we identified two distinct types of dendritic Ca2+ spikes in CA3PCs: ADP-type global Ca2+ spikes promoting CSB firing and a novel, fast Ca2+ spike type that is initiated independently of bAPs and drives single APs. At the soma, compound Ca2+ spikes varied in duration, with long-lasting Ca2+ spikes (~50 ms) supporting plateau potentials and short spikes (few ms long) failing to sustain prolonged depolarization. We revealed that the time course of short spikes is restricted by A- and M- type K+ channels. Cholinergic activation via carbachol and optogenetic stimulation transformed short Ca2+ spikes into prolonged forms and enhanced CSB firing, indicating strong neuromodulatory control over dendritic excitability.
These results uncover the diversity in dendritic Ca2+ spike dynamics among CA3PCs. The ability of cholinergic inputs to modulate Ca2+ spike kinetics and CSB generation suggests a state-dependent mechanism for memory encoding and retrieval within the CA3 network. These findings provide new insights into how CA3 network dynamics support associative learning and may inform future research on therapeutic strategies for memory-related disorders.
