RGD Reference Report - Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats. - Rat Genome Database

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Sex-specific effects of Cacna1c haploinsufficiency on object recognition, spatial memory, and reversal learning capabilities in rats.

Authors: Braun, Moria D  Kisko, Theresa M  Vecchia, Débora Dalla  Andreatini, Roberto  Schwarting, Rainer K W  Wöhr, Markus 
Citation: Braun MD, etal., Neurobiol Learn Mem. 2018 Nov;155:543-555. doi: 10.1016/j.nlm.2018.05.012. Epub 2018 May 23.
RGD ID: 42724470
Pubmed: PMID:29800644   (View Abstract at PubMed)
DOI: DOI:10.1016/j.nlm.2018.05.012   (Journal Full-text)

The CACNA1C gene is strongly implicated in the etiology of multiple major neuropsychiatric disorders, such as bipolar disorder, major depression, and schizophrenia, with cognitive deficits being a common feature. It is unclear, however, by which mechanisms CACNA1C variants advance the risk of developing neuropsychiatric disorders. This study set out to investigate cognitive functioning in a newly developed genetic Cacna1c rat model. Specifically, spatial and reversal learning, as well as object recognition memory were assessed in heterozygous Cacna1c+/- rats and compared to wildtype Cacna1c+/+ littermate controls in both sexes. Our results show that both Cacna1c+/+ and Cacna1c+/- animals were able to learn the rewarded arm configuration of a radial maze over the course of seven days. Both groups also showed reversal learning patterns indicative of intact abilities. In females, genotype differences were evident in the initial spatial learning phase, with Cacna1c+/- females showing hypo-activity and fewer mixed errors. In males, a difference was found during probe trials for both learning phases, with Cacna1c+/- rats displaying better distinction between previously baited and non-baited arms; and regarding cognitive flexibility in favor of the Cacna1c+/+ animals. All experimental groups proved to be sensitive to reward magnitude and fully able to distinguish between novel and familiar objects in the novel object recognition task. Taken together, these results indicate that Cacna1c haploinsufficiency has a minor, but positive impact on (spatial) memory functions in rats.



Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Cacna1cRatcognitive inflexibility sexual_dimorphismIMP compared to male wild-typeRGD 
Cacna1cem1SageRatcognitive inflexibility sexual_dimorphismIMP compared to male wild-typeRGD 
SD-Cacna1cem1SageRatcognitive inflexibility sexual_dimorphismIMP compared to male wild-typeRGD 
Cacna1cRatimpaired spatial learning sexual_dimorphismIMP compared to female wild-typeRGD 
Cacna1cem1SageRatimpaired spatial learning sexual_dimorphismIMP compared to female wild-typeRGD 
SD-Cacna1cem1SageRatimpaired spatial learning sexual_dimorphismIMP compared to female wild-typeRGD 

Genes (Rattus norvegicus)
Cacna1c  (calcium voltage-gated channel subunit alpha1 C) Cacna1cem1Sage  (calcium voltage-gated channel subunit alpha1 C; zinc finger nuclease induced mutant 1, Sigma Advanced Genetic Engineering Labs)

Strains
SD-Cacna1cem1Sage  (NA)