MINI REVIEW article
Front. Cell. Neurosci.
Sec. Cellular Neurophysiology
This article is part of the Research TopicSynaptic Plasticity Across the Lifespan: Mechanisms, Adaptation, and VulnerabilityView all articles
Age dependent seizure susceptibility of CA2 hippocampal neurons
Provisionally accepted
- School of Medicine, St George's University, Saint George's, Grenada
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The hippocampal CA2 region is increasingly recognized as a functionally distinct subfield essential for social recognition memory and the proper routing of information through the hippocampal circuit. Unlike the CA1 and CA3 subfields, CA2 pyramidal neurons show relative sparing from seizure-associated cell loss in many adult models of epilepsy; however, this resilience is not absolute, as recent work demonstrates that CA2 can also exhibit heightened excitability and contribute to seizure propagation under certain models and pathological conditions. Multiple cellular and molecular features—including dense inhibitory interneuron networks, enriched expression of RGS14, PCP4, STEP, perineuronal nets (PNNs), and specialized calcium-handling machinery—collectively constrain synaptic plasticity and reduce excitotoxic vulnerability in mature CA2 neurons. In contrast, these protective mechanisms are underdeveloped during early postnatal periods, rendering the CA2 region more susceptible to hyperexcitation and circuit disruption. Early-life seizures (ELS) occurring within this developmental window may therefore adversely reshape CA2 connectivity and function, potentially altering social memory formation and contributing to later-life cognitive or behavioral impairments. Understanding how CA2 transitions from early vulnerability to adult resilience provides a critical framework for linking developmental epileptogenic insults to long-term deficits in social and mnemonic processing.
Keywords: Hippocampus, CA2, perineuronal nets, age-dependent seizure susceptibility, RGS14, Early-life seizures, postnatal
Received: 29 Sep 2025; Accepted: 27 Nov 2025.
Copyright: © 2025 Correa, Sablani, Wasfi, Correa and Bandelow. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jeff Correa
Stephan Bandelow
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