title: GluA4 subunit of AMPA receptors mediates the early synaptic response to altered network activity in the developing hippocampus.
abstract: Development of the neuronal circuitry involves both Hebbian and homeostatic plasticity mechanisms that orchestrate activity-dependent refinement of the synaptic connectivity. AMPA receptor subunit GluA4 is expressed in hippocampal pyramidal neurons during early postnatal period and is critical for neonatal long-term potentiation; however, its role in homeostatic plasticity is unknown. Here we show that GluA4-dependent plasticity mechanisms allow immature synapses to promptly respond to alterations in network activity. In the neonatal CA3, the threshold for homeostatic plasticity is low, and a 15-h activity blockage with tetrodotoxin triggers homeostatic upregulation of glutamatergic transmission. On the other hand, attenuation of the correlated high-frequency bursting in the CA3-CA1 circuitry leads to weakening of AMPA transmission in CA1, thus reflecting a critical role for Hebbian synapse induction in the developing CA3-CA1. Both of these developmentally restricted forms of plasticity were absent in GluA4(-/-) mice. These data suggest that GluA4 enables efficient homeostatic upscaling and responsiveness to temporal activity patterns during the critical period of activity-dependent refinement of the circuitry.
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland; and.
authors.forename: J
authors.initials: J
authors.lastname: Huupponen
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland; and.
authors.forename: T
authors.initials: T
authors.lastname: Atanasova
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Taira
authors.affiliation: Neuroscience Center, University of Helsinki, Helsinki, Finland; Department of Biosciences, University of Helsinki, Helsinki, Finland; and sari.lauri@helsinki.fi.
authors.forename: S E
authors.initials: SE
authors.lastname: Lauri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002229:Carbenoxolone / Q000494:pharmacology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology* / Q000254:growth & development; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D018091:Receptors, AMPA / Q000172:deficiency* / Q000235:genetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; C104724:glutamate receptor ionotropic, AMPA 4; D013779:Tetrodotoxin; D002229:Carbenoxolone
keywords: GluA4; hippocampus; homeostatic plasticity