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Training-induced changes in the expression of GABAA-associated genes in the amygdala after the acquisition and extinction of Pavlovian fear

期刊

EUROPEAN JOURNAL OF NEUROSCIENCE
卷 26, 期 12, 页码 3631-3644

出版社

WILEY
DOI: 10.1111/j.1460-9568.2007.05970.x

关键词

benzodiazepines; C57BI/6J mice; fear-potentiated startle; GABA

资金

  1. NIDA NIH HHS [R01 DA019624, R01 DA019624-02, DA-019624, R01 DA019624-01A2] Funding Source: Medline
  2. NIMH NIH HHS [F32 MH073389-01, F32 MH073389] Funding Source: Medline

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Previous work suggests the gamma-aminobutyric acid (GABA)ergic system may be dynamically regulated during emotional learning. In the current study we examined training-induced changes in the expression of GABA(A)-related genes and the binding of GABA receptor radioligands in the amygdala after the acquisition and extinction of Pavlovian fear. Using in situ hybridization, we examined the expression pattern changes of mRNAs for GABAergic markers in the lateral, basolateral and central subdivisions of the amygdala in C57Bl/6J mice. These markers included GABA-synthesizing enzymes (GAD67 and GAD65), major GABA(A) receptor subunits (alpha 1, alpha 2, alpha 3, alpha 5, beta 2 and gamma 2) and the expression of mRNAs that are involved in a variety of GABA-related intracellular processes, including GABA transporter-1 (GAT1), GABA(A) receptor-associated protein and the GABA(A) clustering protein, gephyrin. With fear conditioning, we found decreased mRNA levels of alpha 1, alpha 5 and GAD67, as well as deceased benzodiazepine binding in the amygdala. Fear extinction induced an increase in mRNA levels of alpha 2, beta 2, GAD67 and gephyrin, as well as a decrease in GAT1. Together, these findings indicate that the acquisition of fear induced a downregulation of mRNA markers related to a decrease in amygdala GABAergic function, whereas the acquisition of fear extinction produced an upregulation of GABAergic markers related to enhanced GABAergic transmission.

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