GluR2 endocytosis-dependent protein degradation in the amygdala mediates memory updating

Nicole C. Ferrara, Timothy J. Jarome, Patrick K. Cullen, Sabrina A. Orsi, Janine L. Kwapis, Sydney Trask, Shane E. Pullins, Fred J. Helmstetter

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Associations learned during Pavlovian fear conditioning are rapidly acquired and long lasting, providing an ideal model for studying long-term memory formation, storage, and retrieval. During retrieval, these memories can “destabilize” and become labile, allowing a transient “reconsolidation” window during which the memory can be updated, suggesting that reconsolidation could be an attractive target for the modification of memories related to past traumatic experiences. This memory destabilization process is regulated by protein degradation and GluR2-endocytosis in the amygdala. However, it is currently unknown if retrieval-dependent GluR2-endocytosis in the amygdala is critical for incorporation of new information into the memory trace. We examined whether the addition of new information during memory retrieval required GluR2-endocytosis to modify the original memory. The presentation of two foot shocks of weaker intensity during retrieval resulted in GluR2 endocytosis-dependent increase in fear responding on a later test, suggesting modification of the original memory. This increase in fear expression was associated with increased protein degradation and zif268 expression in the same population of cells in the amygdala, indicating increased destabilization processes and cellular activity, and both were lost following blockade of GluR2-endocytosis. These data suggest that the endocytosis of GluR2-containing AMPA receptors in the amygdala regulates retrieval-induced strengthening of memories for traumatic events by modulating cellular destabilization and activity.

Original languageEnglish (US)
Article number5180
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

All Science Journal Classification (ASJC) codes

  • General

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