TY - JOUR
T1 - The C-terminal tails of endogenous GluA1 and GluA2 differentially contribute to hippocampal synaptic plasticity and learning
AU - Zhou, Zikai
AU - Liu, An
AU - Xia, Shuting
AU - Leung, Celeste
AU - Qi, Junxia
AU - Meng, Yanghong
AU - Xie, Wei
AU - Park, Pojeong
AU - Collingridge, Graham L.
AU - Jia, Zhengping
PY - 2018/1
Y1 - 2018/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85037695596&partnerID=8YFLogxK
UR - https://www.nature.com/articles/s41593-018-0116-2
U2 - 10.1038/s41593-017-0030-z
DO - 10.1038/s41593-017-0030-z
M3 - Article (Academic Journal)
C2 - 29230056
SN - 1097-6256
VL - 21
SP - 50
EP - 62
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 1
ER -