# Subicular Astrocytes Govern Seizure‐Impaired Fear Memory

## TL;DR

This study shows that astrocytes in the subiculum play a key role in memory problems caused by seizures, and targeting them could help treat these issues.

## Contribution

The study identifies subicular astrocytes as a novel mediator of seizure-induced fear memory deficits via Ca2+-dependent adenosine signaling.

## Key findings

- Subicular astrocytes hyperactivate during seizures and impair fear memory.
- Blocking astrocyte Ca2+ signaling rescues seizure-induced memory deficits.
- Adenosine signaling through A1 receptors mediates astrocyte-driven cognitive dysfunction.

## Abstract

The mechanisms underlying seizure‐associated cognitive impairment remain incompletely characterized. Emerging evidence positions the subiculum, a hippocampal output hub critically involved in both epileptic seizure and cognitive performance, as a putative nexus for this comorbidity. Here, it is demonstrated that astrocytic activation in the subiculum mediates seizure‐induced fear memory deficits. Subicular astrocytes dynamically respond to conditioned fear memory learning, acting as a “scavenger” for the inhibition of context memory. Seizure activity hyperactivates these leaning‐associated astrocytes and amplifies their engagement during fear processing. Suppression of subicular astrocyte Ca2+ signaling fully rescues seizure‐induced fear memory deficits, while Gq pathway activation in the subicular astrocytes replicates cognitive impairment. Mechanistically, this seizure‐induced astrocyte dysregulation specifically involves Ca2+‐dependent gliotransmitter adenosine‐mediated inhibition through A1 receptors, reducing local neuronal excitability during fear processing. Collectively, these findings identify subicular astrocytes as critical modulators of seizure‐associated cognitive dysfunction, operating through a Ca2+‐dependent adenosine‐linked pathway that disrupts neural circuit homeostasis. This work highlights the potential for astrocyte‐targeted interventions as a therapeutic strategy for seizure‐related memory disorders.

Astrocytes in dorsal subiculum act as a critical modulator of seizure‐associated cognitive dysfunction, operating through a Ca2+‐dependent adenosine‐linked astrocyte‐neuron signaling pathway that disrupts neuronal circuit homeostasis. This research highlights the potential of astrocyte‐targeted interventions as a therapeutic strategy, moving beyond the conventional neuron‐centric view for treating seizure‐related fear memory disorders.