The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampalsynaptic plasticity and learning
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 synaptictransmission, are specifically exchanged. These mice display profound deficits in synaptic plasticity without any effects on basal synaptictransmission. 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.
Authors: Zhou Z1,2,3,4, Liu A3, Xia S1,2,3, Leung C1,2, Qi J3, Meng Y1,2, Xie W3,4, Park P2,5,6, Collingridge GL7,8,9, Jia Z10,11.
Influence Factor: 17.839
Citation: Nat Neurosci 21, 50-62 (2018).