PMCID
PMC12889633

Developmental dysregulation of chandelier cell excitability in a mouse model of Dravet Syndrome.

bioRxiv : the preprint server for biology
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Keywords
Abstract

Chandelier cells (ChCs) are a rare and highly specialized subtype of inhibitory neuron in the cerebral cortex that specifically and exclusively form synapses onto the axon initial segment of excitatory neurons and thereby exert powerful control of excitability. We applied a newly developed, cell type-specific enhancer element to label ChCs and assess their electrophysiological and morphological properties across development in Dravet Syndrome ( mice), a prominent neurodevelopmental disorder defined by epilepsy and features of autism spectrum disorder. Dravet Syndrome is known to predominantly impact GABAergic interneurons. We found that ChCs from juvenile mice (postnatal day, P18-21) exhibit impaired excitability, and that deficits largely persist in young adulthood (P35-56). These findings are distinct from prior observations in the more common subtype of parvalbumin-positive interneurons, basket cells. We found no differences in the axonal or dendritic morphology of ChCs at either time point. Our results suggest a role for ChCs in the pathogenesis of Dravet Syndrome and constitute the first targeted study of ChC function in a specific genetically-defined neurodevelopmental disorder.

Year of Publication
2026
Journal
bioRxiv : the preprint server for biology
Date Published
02/2026
ISSN
2692-8205
DOI
10.64898/2026.02.02.702918
PubMed ID
41676684
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