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Research ArticleNew Research, Neuronal Excitability

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

Jung-Hwa Tao-Cheng, Rita Azzam, Virginia Crocker, Christine A. Winters and Tom Reese
eNeuro 18 November 2015, 2 (6) ENEURO.0066-15.2015; DOI: https://doi.org/10.1523/ENEURO.0066-15.2015
Jung-Hwa Tao-Cheng
1Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892
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Rita Azzam
1Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892
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Virginia Crocker
1Electron Microscopy Facility, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892
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Christine A. Winters
2Laboratory of Neurobiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892
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Tom Reese
2Laboratory of Neurobiology, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892
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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.

  • electron microscopy
  • extrasynaptic
  • NMDA receptors
  • postsynaptic density
  • synapse formation

Footnotes

  • ↵1 The authors declare no competing financial interests.

  • ↵3 This research was supported by intramural funds from the National Institute of Neurological Diseases and Stroke.

This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

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eneuro: 2 (6)
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November/December 2015
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Depolarization of Hippocampal Neurons Induces Formation of Nonsynaptic NMDA Receptor Islands Resembling Nascent Postsynaptic Densities
Jung-Hwa Tao-Cheng, Rita Azzam, Virginia Crocker, Christine A. Winters, Tom Reese
eNeuro 18 November 2015, 2 (6) ENEURO.0066-15.2015; DOI: 10.1523/ENEURO.0066-15.2015

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Depolarization of Hippocampal Neurons Induces Formation of Nonsynaptic NMDA Receptor Islands Resembling Nascent Postsynaptic Densities
Jung-Hwa Tao-Cheng, Rita Azzam, Virginia Crocker, Christine A. Winters, Tom Reese
eNeuro 18 November 2015, 2 (6) ENEURO.0066-15.2015; DOI: 10.1523/ENEURO.0066-15.2015
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Keywords

  • electron microscopy
  • extrasynaptic
  • NMDA receptors
  • postsynaptic density
  • synapse formation

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