title: Depolarization of Hippocampal Neurons Induces Formation of Nonsynaptic NMDA Receptor Islands Resembling Nascent Postsynaptic Densities.
abstract: Depolarization of neurons in 3-week-old rat hippocampal cultures promotes a rapid increase in the density of surface NMDA receptors (NRs), accompanied by transient formation of nonsynaptic NMDA receptor clusters or NR islands. Islands exhibit cytoplasmic dense material resembling that at postsynaptic densities (PSDs), and contain typical PSD components, including MAGUKS (membrane-associated guanylate kinases), GKAP, Shank, Homer, and CaMKII detected by pre-embedding immunogold electron microscopy. In contrast to mature PSDs, islands contain more NMDA than AMPA receptors, and more SAP102 than PSD-95, features that are shared with nascent PSDs in developing synapses. Islands do not appear to be exocytosed or endocytosed directly as preformed packages because neurons lacked intracellular vacuoles containing island-like structures. Islands form and disassemble upon depolarization of neurons on a time scale of 2-3 min, perhaps representing an initial stage in synaptogenesis.
authors.affiliation: Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Tao-Cheng
authors.affiliation: Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Rita
authors.initials: R
authors.lastname: Azzam
authors.affiliation: Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Virginia
authors.identifier: 0000-0001-5416-1473
authors.initials: V
authors.lastname: Crocker
authors.affiliation: Laboratory of Neurobiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Winters
authors.affiliation: Laboratory of Neurobiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health , Bethesda, Maryland 20892.
authors.forename: Tom
authors.initials: T
authors.lastname: Reese
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051528:Guanylate Kinases / Q000032:analysis / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D057907:Post-Synaptic Density / Q000378:metabolism*; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D051528:Guanylate Kinases
keywords: NMDA receptors; electron microscopy; extrasynaptic; postsynaptic density; synapse formation