Depolarization of Hippocampal Neurons Induces Formation of Nonsynaptic NMDA Receptor Islands Resembling Nascent Postsynaptic Densities

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 postsynapti...

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Bibliographic Details
Published in:eNeuro 2015-11, Vol.2 (6), p.ENEURO.0066-15.2015
Main Authors: Tao-Cheng, Jung-Hwa, Azzam, Rita, Crocker, Virginia, Winters, Christine A, Reese, Tom
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Guanylate Kinases - analysis
Guanylate Kinases - physiology
Hippocampus - metabolism
Intracellular Signaling Peptides and Proteins - analysis
Intracellular Signaling Peptides and Proteins - physiology
Mice
Nerve Tissue Proteins - metabolism
Neurons - metabolism
New Research
Post-Synaptic Density - metabolism
Receptors, AMPA - analysis
Receptors, AMPA - metabolism
Receptors, N-Methyl-D-Aspartate - metabolism
Synapses - metabolism
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Summary: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.
ISSN:2373-2822
2373-2822
DOI:10.1523/ENEURO.0066-15.2015