title: Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor.
abstract: Phosphorylation of the GluA1 subunit of AMPA receptors has been proposed to regulate receptor trafficking and synaptic transmission and plasticity. However, it remains unclear whether GluA1 phosphorylation is permissive or sufficient for enacting these functional changes. Here we investigate the role of GluA1 phosphorylation at S831 and S845 residues in the hippocampus through the analyses of GluA1 S831D/S845D phosphomimetic knock-in mice. S831D/S845D mice showed normal total and surface expression and subcellular localization of GluA1 as well as intact basal synaptic transmission. In addition, theta-burst stimulation, a protocol that was sufficient to induce robust long-term potentiation (LTP) in WT mice, resulted in LTP of similar magnitude in S831D/S845D mice. However, S831D/S845D mice showed LTP induced with 10-Hz stimulation, a protocol that is weaker than theta-burst stimulation and was not sufficient to induce LTP in WT mice. Moreover, S831D/S845D mice exhibited LTP induced with spike-timing-dependent plasticity (STDP) protocol at a long pre-post interval that was subthreshold for WT mice, although a suprathreshold STDP protocol at a short pre-post interval resulted in similarly robust LTP for WT and S831D/S845D mice. These results indicate that phosphorylation of GluA1 at S831 and S845 is sufficient to lower the threshold for LTP induction, increasing the probability of synaptic plasticity.
authors.affiliation: Department of Neuroscience and The Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Makino
authors.forename: Richard C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yu
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D006624:Hippocampus; D017774:Long-Term Potentiation; D051379:Mice; D009154:Mutation; D009473:Neuronal Plasticity; D010766:Phosphorylation; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D018091:Receptors, AMPA