Regulation of the expression of the psychiatric risk gene Cacna1c during associative learning

Sykes, L., Clifton, Nicholas ORCID: https://orcid.org/0000-0003-2597-5253, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 and Thomas, Kerrie L. ORCID: https://orcid.org/0000-0003-3355-9583 2018. Regulation of the expression of the psychiatric risk gene Cacna1c during associative learning. Molecular Neuropsychiatry 4 , pp. 149-157. 10.1159/000493917

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Abstract

CACNA1Cencodes the Cav1.2 L-type voltage-gated calcium channel. Generic variation in CACNA1C has been consistently identified as associated with risk for psychiatric disorders including schizophrenia, bipolar disorder, major depressive disorder and autism. Psychiatric risk loci are also enriched for genes involved in the regulation of synaptic plasticity. Here, we show that the expression of Cacna1c is regulated in the rat hippocampus after context exposure, contextual fear conditioning and fear memory retrieval in a manner that correlates to specific memory processes. Using quantitative in situ hybridisation, the expression was down-regulated in CA1 by brief exposure to a novel context and to a conditioned context, and up-regulated in the dentate gyrus after contextual fear conditioning. No changes were measured after prolonged context exposure followed by conditioning, a procedure that retards fear conditioning (latent inhibition), nor with fear memory recall leading to extinction. These results are consistent with a selective role for Cav1.2 in the consolidation of context memory and contextual fear memory, and with processes associated with the maintenance of the fear memory after recall. The dysregulation of CACNA1C may thus be related to associative memory dysfunction in schizophrenia and other psychiatric disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine
Publisher:	Karger Publishers
ISSN:	2296-9209
Date of First Compliant Deposit:	9 October 2018
Date of Acceptance:	19 September 2018
Last Modified:	19 Nov 2024 10:00
URI:	https://orca.cardiff.ac.uk/id/eprint/115689

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