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

Patricia Gasalla, Denise Manahan-Vaughan, Dominic Michael Dwyer, Jeremy Hall, Marta Méndez-Couz

Neuropharmacology 2023 Apr 01

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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. This article is part of the Special Issue on "L-type calcium channel mechanisms in neuropsychiatric disorders". Copyright © 2023 Elsevier Ltd. All rights reserved.

Citation

Patricia Gasalla, Denise Manahan-Vaughan, Dominic Michael Dwyer, Jeremy Hall, Marta Méndez-Couz. Characterisation of the neural basis underlying appetitive extinction & renewal in Cacna1c rats. Neuropharmacology. 2023 Apr 01;227:109444