Cacna1c Hemizygosity Results in Aberrant Fear Conditioning to Neutral Stimuli
Autor: | Kerrie L. Thomas, Nichola M. Brydges, Jeremy Hall, Anna L. Moon, Lawrence Stephen Wilkinson |
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Rok vydání: | 2020 |
Předmět: |
Psychosis
AcademicSubjects/MED00810 salience 03 medical and health sciences 0302 clinical medicine Medicine psychosis Fear conditioning Bipolar disorder 030304 developmental biology 0303 health sciences calcium learning Recall Voltage-dependent calcium channel business.industry medicine.disease animal models Associative learning Psychiatry and Mental health fear Conditioning business Neuroscience 030217 neurology & neurosurgery Regular Articles Psychopathology |
Zdroj: | Schizophrenia Bulletin |
ISSN: | 1745-1701 0586-7614 |
Popis: | 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. |
Databáze: | OpenAIRE |
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