title: Developmental switch in the kinase dependency of long-term potentiation depends on expression of GluA4 subunit-containing AMPA receptors.
abstract: The AMPA-receptor subunit GluA4 is expressed transiently in CA1 pyramidal neurons at the time synaptic connectivity is forming, but its physiological significance is unknown. Here we show that GluA4 expression is sufficient to alter the signaling requirements of long-term potentiation (LTP) and can fully explain the switch in the LTP kinase dependency from PKA to Ca2(+)/calmodulin-dependent protein kinase II during synapse maturation. At immature synapses, activation of PKA leads to a robust potentiation of AMPA-receptor function via the mobilization of GluA4. Analysis of GluA4-deficient mice indicates that this mechanism is critical for neonatal PKA-dependent LTP. Furthermore, lentiviral expression of GluA4 in CA1 neurons conferred a PKA-dependent synaptic potentiation and LTP regardless of the developmental stage. Thus, GluA4 defines the signaling requirements for LTP and silent synapse activation during a critical period of synapse development.
authors.affiliation: Neuroscience Center, Department of Biosciences, Division of Physiology and Neuroscience and Division of Biochemistry and Biotechnology, and Department of Veterinary Biosciences, University of Helsinki, 00014, Helsinki, Finland.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Luchkina
authors.forename: Johanna
authors.initials: J
authors.lastname: Huupponen
authors.forename: Vernon R J
authors.initials: VR
authors.lastname: Clarke
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Coleman
authors.forename: Kari
authors.initials: K
authors.lastname: Keinänen
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
authors.forename: Sari E
authors.initials: SE
authors.lastname: Lauri
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D016086:Lentivirus; D017774:Long-Term Potentiation / Q000502:physiology*; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: glutamate receptor; hippocampus; synaptic transmission