The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning

Zikai Zhou, An Liu, Shuting Xia, Celeste Leung, Junxia Qi, Yanghong Meng, Wei Xie, Pojeong Park, Graham L. Collingridge*, Zhengping Jia

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

43 Citations (Scopus)
360 Downloads (Pure)

Abstract

Long-term potentiation (LTP) and depression (LTD) at glutamatergic synapses are intensively investigated processes for understanding the synaptic basis for learning and memory, but the underlying molecular mechanisms remain poorly understood. We have made three mouse lines where the C-terminal domains (CTDs) of endogenous AMPA receptors (AMPARs), the principal mediators of fast excitatory synaptic transmission, are specifically exchanged. These mice display profound deficits in synaptic plasticity without any effects on basal synaptic transmission. Our study reveals that the CTDs of GluA1 and GluA2, the key subunits of AMPARs, are necessary and sufficient to drive NMDA receptor-dependent LTP and LTD, respectively. In addition, these domains exert differential effects on spatial and contextual learning and memory. These results establish dominant roles of AMPARs in governing bidirectional synaptic and behavioral plasticity in the CNS.

Original languageEnglish
Pages (from-to)50-62
Number of pages16
JournalNature Neuroscience
Volume21
Issue number1
Early online date11 Dec 2017
DOIs
Publication statusPublished - Jan 2018

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