Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome

Craddock, Rosie, Tigaret, Cezar M. ORCID: https://orcid.org/0000-0001-5848-6697 and Sengpiel, Frank ORCID: https://orcid.org/0000-0002-7060-1851 2025. Disruptions in primary visual cortex physiology and function in a mouse model of Timothy syndrome. Cerebral Cortex 35 (6) , bhaf162. 10.1093/cercor/bhaf162

PDF - Published Version Available under License Creative Commons Attribution. Download (1MB)

Abstract

Timothy syndrome (TS) is a rare genetic disorder caused by mutations in the CACNA1C gene, which encodes the L-type calcium channel α1 CaV1.2 subunit. While it is expressed throughout the body, the most serious symptoms are cardiac and neurological. Classical TS type 1 (TS1) and TS type 2 (TS2) mutations cause prolonged action potentials (APs) in cardiomyocytes and in induced neurons derived from pluripotent stem cells taken from TS patients, but the effects of TS mutations on neuronal function in vivo are not fully understood. TS is frequently associated with autistic traits, which in turn have been linked to altered sensory processing. Using the TS2-neo mouse model, we analyzed the effects of TS2 mutation on the visual system. We observed a widening of APs of pyramidal cells in ex vivo patch clamp recordings and an increase in the density of parvalbumin-positive cells in the primary visual cortex. Neurons from TS2-neo mice recorded extracellularly in vivo were less likely to respond to visual stimuli of low spatial frequency, but more likely to respond to visual stimuli of mid-to-high spatial frequency, compared to those from wild-type mice. These results point to a basic processing abnormality in the visual cortex of TS2-neo mice.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine Schools > Biosciences ?? NMHII ??
Publisher:	Oxford University Press
ISSN:	1047-3211
Date of First Compliant Deposit:	3 June 2025
Date of Acceptance:	2 June 2025
Last Modified:	17 Jul 2025 13:29
URI:	https://orca.cardiff.ac.uk/id/eprint/178726

Actions (repository staff only)

Edit Item