GABAA receptor endocytosis in the basolateral amygdala is critical to the reinstatement of fear memory measured by fear-potentiated startle

Hui Ching Lin, Yu Chou Tseng, Sheng Chun Mao, Po See Chen, Po Wu Gean

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Reinstatement represents a phenomenon that may be used to model the effects of retraumatization observed in patients with posttraumatic stress disorder (PTSD). In this study, we found intraperitoneal injection of the β-adrenergic receptor antagonist propranolol (10 mg/kg) 1 h before reinstatement training attenuated reinstatement of fear memory in rats. Conversely, reinstatement was facilitated by intra-amygdalar administration of β-adrenergic receptor agonist isoproterenol (Iso; 2 μg per side) 30 min before reinstatement training. The frequency and amplitude of the miniature IPSC (mIPSC) and the surface expression of the β33 and γ2 subunits of the GABAA receptor (GABAAR) were significantly lower in reinstated than in extinction rats, whereas the AMPA/NMDA ratio and the surface expression of GluR1 and GluR2 in the amygdala did not differ between groups. In amygdala slices, Iso-induced decrease in the surface β3 subunit of GABAA receptor was blocked by a Tat-conjugated dynamin function-blocking peptide (Tat-P4) pretreatment (10 μm for 30 min). By contrast, Tat-scramble peptide had no effect. Intravenous injection (3 μmol/kg) or intra-amygdalar infusion (30 pmol per side) of Tat-P4 interfered with reinstatement. Reinstatement increased the association between protein phosphatase 2A (PP2A) and the β33 subunit of the GABAAR, which was abolished by PP1/PP2A inhibitors okadaic acid and calyculin A. These results suggest the involvement of (β-adrenergic receptor activation and GABAA receptor endocytosis in the amygdala for the reinstatement in fear memory.

Original languageEnglish
Pages (from-to)8851-8861
Number of pages11
JournalJournal of Neuroscience
Volume31
Issue number24
DOIs
Publication statusPublished - 2011 Jun 15

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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