Characterisation of the neural basis underlying appetitive extinction & renewal in a Cacna1c rats

Gasalla Canto, Patricia, Manahan-Vaughan, Denise, Dwyer, Dominic Michael ORCID: https://orcid.org/0000-0001-8069-5508, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009 and Méndez-Couz, Marta 2023. Characterisation of the neural basis underlying appetitive extinction & renewal in a Cacna1c rats. Neuropharmacology 227 , 109444. 10.1016/j.neuropharm.2023.109444

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Abstract

Recent studies have revealed impairments in Cacna1c ± heterozygous animals (a gene that encodes the Cav 1.2 L-type voltage-gated calcium channels and is implicated in risk for multiple neuropsychiatric disorders) in aversive forms of learning, such as latent inhibition, reversal learning or context discrimination. However, the role of Cav 1.2 L-type voltage-gated calcium channels in extinction of appetitive associations remains under-investigated. Here, we used an appetitive Pavlovian conditioning task and evaluated extinction learning (EL) with a change of context from that of training and test (ABA) and without such a change (AAA) in Cacna1c ± male rats versus their wild-type (WT) littermates. In addition, we used fluorescence in situ hybridization of somatic immediate early genes (IEGs) Arc and Homer1a expression to scrutinize associated changes in the medial prefrontal cortex and the amygdala. Cacna1c ± animals successfully adapt their responses by engaging in appetitive EL and renewal. However, the regional IEG expression profile changed. For the EL occurring in the same context, Cacna1c ± animals presented higher IEG expression in the infralimbic cortex and the central amygdala than controls. The prelimbic region presented a larger neural ensemble in Cacna1c ± than WT animals, co-labelled for the time window of EL in the original context and prolonged exposure to the unrewarded context. With a context change, the Cacna1c ± infralimbic region displayed higher IEG expression during renewal than controls. Taken together, our findings provide novel evidence of distinct brain activation patterns occurring in Cacna1c ± rats after appetitive extinction and renewal despite preserved behavioral responses.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Neuroscience and Mental Health Research Institute (NMHRI) Psychology
Publisher:	Elsevier
ISSN:	0028-3908
Date of First Compliant Deposit:	17 February 2023
Date of Acceptance:	25 January 2023
Last Modified:	27 Feb 2024 18:42
URI:	https://orca.cardiff.ac.uk/id/eprint/157122

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