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Title: KCNQ2 channels regulate the population activity of neonatal GABAergic neurons ex vivo
Over the last decade KCNQ2 channels have arisen as fundamental and indispensable regulators of neonatal brain excitability, with KCNQ2 loss-of-function pathogenic variants being increasingly identified in patients with developmental and epileptic encephalopathy. However, the mechanisms by which KCNQ2 loss-of-function variants lead to network dysfunction are not fully known. An important remaining knowledge gap is whether loss of KCNQ2 function alters GABAergic interneuron activity early in development. To address this question, we applied mesoscale calcium imagingex vivoin postnatal day 4–7 mice lacking KCNQ2 channels in interneurons (Vgat-ires-cre;Kcnq2f/f;GCamp5). In the presence of elevated extracellular potassium concentrations, ablation of KCNQ2 channels from GABAergic cells increased the interneuron population activity in the hippocampal formation and regions of the neocortex. We found that this increased population activity depends on fast synaptic transmission, with excitatory transmission promoting the activity and GABAergic transmission curtailing it. Together, our data show that loss of function of KCNQ2 channels from interneurons increases the network excitability of the immature GABAergic circuits, revealing a new function of KCNQ2 channels in interneuron physiology in the developing brain.  more » « less
Award ID(s):
1845348
PAR ID:
10525428
Author(s) / Creator(s):
; ;
Publisher / Repository:
Frontiers in Science
Date Published:
Journal Name:
Frontiers in Neurology
Volume:
14
ISSN:
1664-2295
Subject(s) / Keyword(s):
KCNQ2 epilepsy neurological disorders channelopathy neonate
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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