Extinction training in conjunction with a partial agonist of the glycine site on the NMDA receptor erases memory trace

Sheng Chun Mao, Ya Hsin Hsiao, Po Wu Gean

Research output: Contribution to journalArticlepeer-review

94 Citations (Scopus)

Abstract

Much evidence indicates that extinction training does not erase memory traces but instead forms inhibitory learning that prevents the expression of original memory. Fear conditioning induces long-term potentiation and drives synaptic insertion of AMPA receptors into the amygdala. Here we show that extinction training applied 1 h after training reversed the conditioning-induced increase in surface glutamate receptor subunit 1 (GluR1) in parallel with the inhibition of startle potentiation. However, if applied 24 h after training, extinction training reduced startle potentiation without influencing the GluR1 increase. We infused D-cycloserine (DCS), a partial agonist of the glycine site on the NMDA receptor, bilaterally into the amygdala 30 min before extinction training. This augmented the extinction training-elicited reduction in startle and reversed the conditioning-induced increase in GluR1. Delivery of five sets of tetanic stimulation (TS) to the external capsule produced a robust enhancement of synaptic responses in the lateral amygdala neurons that persisted for >2 h. Low-frequency stimulation applied 1 h after TS had no long-lasting effect on synaptic responses. The same treatments, however, induced depotentiation in the presence of DCS and reversed TS-induced increase in surface GluR1. Together, this study has two important findings: (1) whether a memory trace remains intact or is erased depends on the interval between conditioning and extinction training and (2) DCS facilitates the reversal of memory trace. DCS-induced augmentation of extinction and reversal of GluR1 surface expression are likely mediated by DCS-facilitated endocytosis of AMPA receptors.

Original languageEnglish
Pages (from-to)8892-8899
Number of pages8
JournalJournal of Neuroscience
Volume26
Issue number35
DOIs
Publication statusPublished - 2006 Aug 30

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Extinction training in conjunction with a partial agonist of the glycine site on the NMDA receptor erases memory trace'. Together they form a unique fingerprint.

Cite this