title: Extinction training in conjunction with a partial agonist of the glycine site on the NMDA receptor erases memory trace.
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.
authors.affiliation: Institute of Basic Medical Sciences and Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan 701, Taiwan.
authors.forename: Sheng-Chun
authors.initials: SC
authors.lastname: Mao
authors.forename: Ya-Hsin
authors.initials: YH
authors.lastname: Hsiao
authors.forename: Po-Wu
authors.initials: PW
authors.lastname: Gean
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D003213:Conditioning, Psychological; D003523:Cycloserine / Q000494:pharmacology*; D004597:Electroshock; D005108:Extinction, Psychological; D005998:Glycine / Q000378:metabolism*; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D003523:Cycloserine; D005998:Glycine; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate