title: Synaptic Consolidation Normalizes AMPAR Quantal Size following MAGUK Loss.
abstract: The mechanisms controlling synapse growth and maintenance are of critical importance for learning and memory. The MAGUK family of synaptic scaffolding proteins is abundantly expressed at glutamatergic central synapses, but their importance in controlling the synaptic content of glutamate receptors is poorly understood. Here, we use a chained RNAi-mediated knockdown approach to simultaneously remove PSD-93, PSD-95, and SAP102, the MAGUKs previously shown to be responsible for synaptic localization of glutamate receptors. We find that MAGUKs are specifically responsible for creating functional synapses after initial spine formation by filling functionally silent spines with glutamate receptors. Removal of the MAGUKs causes a transient reduction in AMPA receptor quantal size followed by synaptic consolidation resulting in a normalization of quantal size at the few remaining functional synapses. Consolidation requires signaling through L-type calcium channels, CaM kinase kinase, and the GluA2 AMPA receptor subunit, akin to a homeostatic process.
authors.affiliation: Neuroscience Graduate Program, University of California San Francisco, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Levy
authors.affiliation: Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Neurobiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Reese
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA 94158, USA. Electronic address: roger.nicoll@ucsf.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency* / Q000235:genetics; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D009479:Neuropeptides / Q000172:deficiency* / Q000235:genetics; D009924:Organ Culture Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C101195:Dlg3 protein, rat; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C501451:Mpp2 protein, rat; D009479:Neuropeptides; D018091:Receptors, AMPA