Block of γ-Aminobutyric Acid-A Receptor Insertion in the Amygdala Impairs Extinction of Conditioned Fear

Hui Ching Lin, Sheng Chun Mao, Po Wu Gean

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Background: Extinction is a complex phenomenon but generally is regarded as a new inhibitory learning that suppresses the original memory. However, how or from where the inhibition originates remains to be determined. In the present study, we examine whether increase in the expression of γ-aminobutyric acid (GABA)A receptors in the amygdala is required for extinction by employing cell-permeable TAT-conjugated peptide (TAT)-GABA receptor-associated protein (GABARAP) inhibitory peptide to block GABAA receptor insertion. Methods: Retention of fear memory was assessed with fear-potentiated startle paradigm. Whole cell patch clamp recordings were performed to record miniature inhibitory postsynaptic current (mIPSC). Western blotting analysis was used to measure the expression of gephyrin, β2, and γ2 subunits of GABAA receptor. Results: Fear conditioning decreased frequency and amplitude of mIPSC and surface protein levels of β2 and γ2 subunits of GABAA receptor. Extinction training, by contrast, reversed the decreased frequency and amplitude of mIPSC and surface protein levels of gephyrin and β2 subunit of GABAA receptor. Disruption of GABARAP-GABAA receptor interaction in the amygdala with GABARAP inhibitory peptide blocked N-methyl-D-aspartate-mediated GABAA receptor insertion in the amygdala. Importantly, it also blocked extinction-induced increase in the frequency and amplitude of mIPSCs, and the reduction of fear-potentiated startle. Conclusions: GABAA receptor insertion in the amygdala contributes a significant part to the extinction of fear memory.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalBiological Psychiatry
Volume66
Issue number7
DOIs
Publication statusPublished - 2009 Oct 1

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

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