Synaptic plasticity deficits in a mouse model of Timothy syndrome: LTP saturation and its pharmacological rescue by nifedipine.

ABSTRACT: Timothy syndrome (TS) is a multisystem disorder characterized by cardiovascular abnormalities and a spectrum of neuropsychiatric symptoms, including language impairment, seizure, cognitive disability and autism. TS is caused by gain of function mutations in the CACNA1C gene that encodes the CaV1.2 L-type calcium channel. TS mutations have been reported to disrupt hippocampal long-term potentiation (LTP), a process implicated in memory formation. Here, we compared wild type (WT) and heterozygous G406R CaV1.2 mutant TS2-neo model mice using a LTP saturation protocol consisting of two successive theta burst stimuli. While WT mice showed potentiated synaptic strength in response to both theta-burst stimuli, TS2-neo mutants exhibited a smaller initial LTP and minimal responses to the second sti

SUBMITTER: Lado W 

PROVIDER: S-EPMC12744305 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature