Regulation of the Expression of the Psychiatric Risk Gene <b><i>Cacna1c</i></b> during Associative Learning

Abstract

CACNA1Cencodes the Ca_v1.2 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 Ca_v1.2 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.

Language impairment with a microduplication in 1q42.3q43

“…Variants of CACNA1C have been associated to deficits in reversal learning (Sykes et al, 2019), whereas some polymorphisms have been associated to decreased semantic verbal fluency in healthy subjects (Krug et al, 2010), as well as to decreased executive function in people with BD (Soeiro- de-Souza et al, 2013). CACNA1C expression has been found modulated during associative learning (Sykes et al, 2018). In mice, deletion of CACNA1C in glutamatergic neurons gives rise to reduced synaptic plasticity, sociability, and cognition (Dedic et al, 2018).…”