title: Molecular mechanisms controlling synaptic recruitment of GluA4 subunit-containing AMPA-receptors critical for functional maturation of CA1 glutamatergic synapses.
abstract: Synaptic recruitment of AMPA receptors (AMPARs) represents a key postsynaptic mechanism driving functional development and maturation of glutamatergic synapses. At immature hippocampal synapses, PKA-driven synaptic insertion of GluA4 is the predominant mechanism for synaptic reinforcement. However, the physiological significance and molecular determinants of this developmentally restricted form of plasticity are not known. Here we show that PKA activation leads to insertion of GluA4 to synaptic sites with initially weak or silent AMPAR-mediated transmission. This effect depends on a novel mechanism involving the extreme C-terminal end of GluA4, which interacts with the membrane proximal region of the C-terminal domain to control GluA4 trafficking. In the absence of GluA4, strengthening of AMPAR-mediated transmission during postnatal development was significantly delayed. These data suggest that the GluA4-mediated activation of silent synapses is a critical mechanism facilitating the functional maturation of glutamatergic circuitry during the critical period of experience-dependent fine-tuning. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
authors.affiliation: Neuroscience Center, University of Helsinki, Finland; Department of Biosciences, University of Helsinki, Finland.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Luchkina
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Coleman
authors.affiliation: Neuroscience Center, University of Helsinki, Finland; Department of Biosciences, University of Helsinki, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Huupponen
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Cai
authors.affiliation: Neuroscience Center, University of Helsinki, Finland.
authors.forename: Anna
authors.initials: A
authors.lastname: Kivistö
authors.affiliation: Neuroscience Center, University of Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Finland.
authors.forename: Tomi
authors.initials: T
authors.lastname: Taira
authors.affiliation: Department of Biosciences, University of Helsinki, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Keinänen
authors.affiliation: Neuroscience Center, University of Helsinki, Finland; Department of Biosciences, University of Helsinki, Finland. Electronic address: sari.lauri@helsinki.fi.
authors.forename: Sari E
authors.initials: SE
authors.lastname: Lauri
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000254:growth & development / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D061251:Primary Cell Culture; D021122:Protein Subunits / Q000378:metabolism; D021381:Protein Transport; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D021122:Protein Subunits; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; D018698:Glutamic Acid; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: AMPA –receptor; Development; GluA4; Silent synapse; Synaptic targeting