title: Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory.
abstract: 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.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Hey-Kyoung
authors.initials: HK
authors.lastname: Lee
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Han
authors.forename: Hengye
authors.initials: H
authors.lastname: Man
authors.forename: Chong-Hyun
authors.initials: CH
authors.lastname: Kim
authors.forename: Gavin
authors.initials: G
authors.lastname: Rumbaugh
authors.forename: Sandy
authors.initials: S
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.forename: Chun
authors.initials: C
authors.lastname: He
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Wenthold
authors.forename: Michela
authors.initials: M
authors.lastname: Gallagher
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: 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*
chemical_list: D018091:Receptors, AMPA