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ALPHA5 SUBUNIT–CONTAINING GABA<SUB>A</SUB> RECEPTORS SELECTIVELY FACILITATE ASYNCHRONOUS NETWORK ACTIVITY IN DEVELOPING MOUSE CA1
Lissy Liebeskindand 6 co-authors
University of Würzburg
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-027
Presentation
Date TBA
Board: PS01-07AM-027
Event Information
Poster Board
PS01-07AM-027
Poster
View posterAbstract
Spontaneous activity is a fundamental feature of developing neuronal circuits and is conserved across brain regions and mammalian species. In the developing hippocampus, it occurs in two distinct modes: synchronous network bursts (NBs) and asynchronous events (AEs). These activity patterns likely serve distinct developmental functions and may therefore be regulated by distinct mechanisms. Employing a combination of multi-neuronal Ca2+ imaging, patch-clamp electrophysiology and scRNA-seq, we show that α5 subunit–containing GABAA receptors (α5-GABAARs) are broadly expressed in neonatal CA1 neurons overlapping with the chloride transporters KCC2 and NKCC1. Functionally, α5-GABAARs selectively enhance AEs while having little impact on NBs. This effect is likely mediated by tonic GABAergic signaling, whereas quantal synaptic currents are independent of α5-GABAARs. Pharmacological blockade of chloride extrusion via KCC2 enhanced NBs but reduced AEs, whereas inhibition of chloride uptake through NKCC1 diminished both activity modes. Together, these findings identify α5-GABAARs as key regulators of neonatal CA1 network dynamics that, in concert with KCC2 and NKCC1, differentially control synchronous and asynchronous activity patterns that shape developing hippocampal circuits.
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