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PMID: 17626197 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Distinct structural and ionotropic roles of NMDA receptors in controlling spine and synapse stability.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 27 ·No. 28 ·2007-07-11 ·Pages 7365-76

Alvarez VA, Ridenour DA, Sabatini BL

Abstract

NMDA-type glutamate receptors (NMDARs) play a central role in the rapid regulation of synaptic transmission, but their contribution to the long-term stabilization of glutamatergic synapses is unknown. We find that, in hippocampal pyramidal neurons in rat organotypic slices, pharmacological blockade of NMDARs does not affect synapse formation and dendritic spine growth but does increase the motility of spines. Physical loss of synaptic NMDARs induced by RNA interference against the NR1 subunit of the receptor also increases the motility of spines. Furthermore, knock-down of NMDARs, but not their pharmacological block, destabilizes spine structure and over time leads to loss of spines and excitatory synapses. Maintenance of normal spine density requires the coexpression of two specific splice isoforms of the NR1 subunit that contain the C-terminal C2 cassette. Thus, although ionotropic properties of NMDARs induce synaptic plasticity, it is the physical interactions of the C-tail of the receptor that mediate the long-term stabilization of synapses and spines.

MeSH Terms
Animals Dendritic Spines/physiology,ultrastructure Disks Large Homolog 4 Protein Electric Conductivity Excitatory Postsynaptic Potentials Hippocampus/cytology,physiology,ultrastructure In Vitro Techniques Intracellular Signaling Peptides and Proteins/metabolism Membrane Proteins/metabolism Neuronal Plasticity/physiology Pyramidal Cells/metabolism,physiology,ultrastructure RNA Interference Rats Rats, Sprague-Dawley Receptors, AMPA/metabolism Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors,genetics,physiology Signal Transduction/physiology Synapses/metabolism,physiology
Chemicals
Disks Large Homolog 4 Protein Dlg4 protein, rat Intracellular Signaling Peptides and Proteins Membrane Proteins NR1 NMDA receptor Receptors, AMPA Receptors, N-Methyl-D-Aspartate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Alvarez Veronica A
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ridenour Dennis A
Sabatini Bernardo L
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0956-07.2007
Published
2007-07-11
Pages
7365-76
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6672602
Subset
IM
Grants
NINDS NIH HHS · R01 NS046579 · United States
NINDS NIH HHS · T32 NS007484 · United States
NINDS NIH HHS · 5T32 NS07484 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0956-07.2007 PMC Full Text View journal details
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