Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.
Plasticity of the nervous system is dependent on mechanisms that regulate the strength of synaptic transmission. Excitatory synapses in the brain undergo long-term potentiation (LTP) and long-term depression (LTD), cellular models of learning and memory. Protein phosphorylation is required for the induction of many forms of synaptic plasticity, including LTP and LTD. However, the critical kinase substrates that mediate plasticity have not been identified. We previously reported that phosphorylation of the GluR1 subunit of AMPA receptors, which mediate rapid excitatory transmission in the brain, is modulated during LTP and LTD. To test if GluR1 phosphorylation is necessary for plasticity and learning and memory, we generated mice with knockin mutations in the GluR1 phosphorylation sites. The phosphomutant mice show deficits in LTD and LTP and have memory defects in spatial learning tasks. These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories.
Lee
Hey-Kyoung
HK
Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Takamiya
Kogo
K
Han
Jung-Soo
JS
Man
Hengye
H
Kim
Chong-Hyun
CH
Rumbaugh
Gavin
G
Yu
Sandy
S
Ding
Lin
L
He
Chun
C
Petralia
Ronald S
RS
Wenthold
Robert J
RJ
Gallagher
Michela
M
Huganir
Richard L
RL
D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D017774:Long-Term Potentiation / Q000235:genetics*; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D008297:Male; D008569:Memory Disorders / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D021381:Protein Transport / Q000235:genetics; D018091:Receptors, AMPA / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*
D018091:Receptors, AMPA