Calcineurin requirement for in vivo insular cortex LTD and CTA-extinction

• Published in: Neurobiology of learning and memory 2022-09, Vol.193, p.107647-107647, Article 107647
• Main Authors: Reyes-García, Salma E., Gutiérrez-Vera, Beatriz, Escobar, Martha L.
• Format: Article
• Language: English
• Subjects: Calcineurin; Extinction; Long-term depression; Synaptic Plasticity
• ISSN: 1074-7427; 1095-9564
• DOI: 10.1016/j.nlm.2022.107647

•Calcineurin inhibition slows down the CTA-extinction.•Calcineurin inhibition blocks the maintenance of LTD.•CaN levels increase after LTD induction. Currently, it is widely accepted that memory extinction involves the formation of a new associative memory rather than unlearning of the information previously acquired. Nonetheless, the cellular and molecular mechanisms underlying this process are still unclear. In this regard, it has been suggested that while kinases modulate conditioning and LTP, phosphatases are relevant for extinction and LTD. In particular, the protein phosphatase calcineurin (CaN) has been involved in the extinction of some behavioral tasks along with LTD. Indeed, studies of our research group have demonstrated that induction of LTD in the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC) pathway facilitates the extinction of conditioned taste aversion (CTA), while the induction of LTP in this pathway slows it down. In addition, we have shown that the extinction of CTA elicits an increase of CaN. The aim of the present study was to evaluate the participation of calcineurin in the extinction of CTA and in the expression of in vivo LTD in the Bla-IC pathway. For this purpose, we chemically inhibited calcineurin in the IC of adult male Wistar rats, either during CTA-extinction or thirty minutes after LTD induction in the Bla-IC pathway. Our results show that calcineurin inhibition slows down the CTA-extinction and blocks the maintenance of LTD. Furthermore, we show that CaN levels increase after LTD induction. These findings support the idea that calcineurin is a key molecular actor for both CTA extinction and LTD expression in the IC, a highly relevant neocortical area for the processing of aversively motivated learning tasks, suggesting that both processes are associated at a molecular level.