Work

Input‐specific bidirectional regulation of hippocampal CA3 pyramidal cell excitability

Year: 2025

Type: article

Abstract: High‐frequency mossy fibre (MF) inputs trigger a sustained increase in excitability to perforant pathway (PP) inputs in CA3 pyramidal cells (CA3‐PC) by reducing Kv1.2 levels at distal apical dendrites, known as long‐term potentiation of intrinsic excitability (LTP‐IE). LTP‐IE enhances excitatory postsynaptic potential (EPSP)‐to‐spike coupling at PP synapses, facilitating Hebbian LTP of synaptic weights. Prolonged hyperexcitability is detrimental, yet it is little understood how LTP‐IE is restored in CA3‐PCs. Here we show that MF‐induced LTP‐IE can be reversed through the burst firing of a CA3‐PC elicited by PP or recurrent synaptic inputs. This reversal was impeded by the oxidative bias of cellular redox state or intracellular Zn 2+ signalling. Because high‐frequency PP inputs to MF‐primed CA3 pyramidal cells not only induce homosynaptic LTP but also restore hyperexcitability, this input‐specific bidirectional regulation of intrinsic excitability may provide a cellular basis for understanding ensemble dynamics in the CA3 network. image Key points Intrinsic excitability plays a pivotal role in recruiting principal cells to neuronal memory ensembles. Mossy fibre inputs prime hippocampal CA3 pyramidal cells by enhancing their intrinsic excitability and excitatory postsynaptic potential (EPSP)‐to‐spike coupling at perforant path (PP) synapses. High‐frequency PP inputs to such primed cells not only induce long‐term potentiation of synaptic weights but also restore the high excitability state to baseline. This input‐specific bidirectional regulation of intrinsic excitability may offer a cellular basis for understanding the ensemble dynamics in the hippocampal CA3 network.

Source: The Journal of Physiology

DOI: 10.1113/jp288350

Authors: Kisang Eom, Yujin Kim, Suk‐Ho Lee

Institution: Seoul National University

Language: English

Topic: Neuroscience and Neuropharmacology Research

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,400