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Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli
CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505182/ https://www.ncbi.nlm.nih.gov/pubmed/31910256 http://dx.doi.org/10.1093/schbul/sbz127 |
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author | Moon, Anna L Brydges, Nichola M Wilkinson, Lawrence S Hall, Jeremy Thomas, Kerrie L |
author_facet | Moon, Anna L Brydges, Nichola M Wilkinson, Lawrence S Hall, Jeremy Thomas, Kerrie L |
author_sort | Moon, Anna L |
collection | PubMed |
description | CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c(+/−)) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c(+/−) rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c(+/−) rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c(+/−) rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis. |
format | Online Article Text |
id | pubmed-7505182 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-75051822020-09-28 Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli Moon, Anna L Brydges, Nichola M Wilkinson, Lawrence S Hall, Jeremy Thomas, Kerrie L Schizophr Bull Regular Articles CACNA1C, a gene that encodes an alpha-1 subunit of L-type voltage-gated calcium channels, has been strongly associated with psychiatric disorders including schizophrenia and bipolar disorder. An important objective is to understand how variation in this gene can lead to an increased risk of psychopathology. Altered associative learning has also been implicated in the pathology of psychiatric disorders, particularly in the manifestation of psychotic symptoms. In this study, we utilize auditory-cued fear memory paradigms in order to investigate whether associative learning is altered in rats hemizygous for the Cacna1c gene. Cacna1c hemizygous (Cacna1c(+/−)) rats and their wild-type littermates were exposed to either delay, trace, or unpaired auditory fear conditioning. All rats received a Context Recall (24 h post-conditioning) and a Cue Recall (48 h post-conditioning) to test their fear responses. In the delay condition, which results in strong conditioning to the cue in wild-type animals, Cacna1c(+/−) rats showed increased fear responses to the context. In the trace condition, which results in strong conditioning to the context in wild-type animals, Cacna1c(+/−) rats showed increased fear responses to the cue. Finally, in the unpaired condition, Cacna1c(+/−) rats showed increased fear responses to both context and cue. These results indicate that Cacna1c heterozygous rats show aberrantly enhanced fear responses to inappropriate cues, consistent with key models of psychosis. Oxford University Press 2020-01-07 /pmc/articles/PMC7505182/ /pubmed/31910256 http://dx.doi.org/10.1093/schbul/sbz127 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Regular Articles Moon, Anna L Brydges, Nichola M Wilkinson, Lawrence S Hall, Jeremy Thomas, Kerrie L Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title |
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title_full |
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title_fullStr |
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title_full_unstemmed |
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title_short |
Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli |
title_sort | cacna1c hemizygosity results in aberrant fear conditioning to neutral stimuli |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505182/ https://www.ncbi.nlm.nih.gov/pubmed/31910256 http://dx.doi.org/10.1093/schbul/sbz127 |
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