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PMID: 11818568 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons.

Vanderklish PW, Edelman GM

Abstract

Changes in the morphology of dendritic spines are correlated with synaptic plasticity and may relate mechanistically to its expression and stabilization. Recent work has shown that spine length can be altered by manipulations that affect intracellular calcium, and spine length is abnormal in genetic conditions affecting protein synthesis in neurons. We have investigated how ligands of group 1 metabotropic glutamate receptors (mGluRs) affect spine shape; stimulation of these receptors leads both to calcium release from intracellular stores and to dendritic protein synthesis. Thirty-minute incubation of cultured hippocampal slices and dissociated neurons with the selective group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced a significant increase in the average length of dendritic spines. This elongation resulted mainly from the growth of existing spines and was also seen even in the presence of antagonists of ionotropic receptors, indicating that activation of these receptors by mGluR-induced glutamate release was not required. Prolonged antagonism of group 1 mGluRs with (S)-alpha-methyl-4-carboxyphenylglycine (MCPG) did not result in shorter average spine length. Elongation of dendritic spines induced by DHPG was blocked by calcium chelation and by preincubation with the protein synthesis inhibitor puromycin. The results suggest that in vivo activation of group 1 mGluRs by synaptically released glutamate affects spine shape in a protein synthesis-dependent manner.

MeSH Terms
6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology Animals Biolistics Cells, Cultured Chelating Agents/pharmacology Dendrites/drug effects,physiology,ultrastructure Egtazic Acid/analogs & derivatives,pharmacology Genes, Reporter Hippocampus/physiology Methoxyhydroxyphenylglycol/analogs & derivatives,pharmacology Neurons/cytology,physiology Organ Culture Techniques Receptors, Metabotropic Glutamate/drug effects,physiology Transfection
Chemicals
Chelating Agents Receptors, Metabotropic Glutamate metabotropic glutamate receptor type 1 Egtazic Acid Methoxyhydroxyphenylglycol 6-Cyano-7-nitroquinoxaline-2,3-dione 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid 3,4-dihydroxyphenylglycol
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Vanderklish Peter W
Department of Neurobiology, The Scripps Research Institute 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. pvanderk@scripps.edu
Edelman Gerald M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2002-02-05
Epub
2002-00-29
Pages
1639-44
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC122243
Subset
IM
Grants
NIMH NIH HHS · K01 MH064036 · United States
NINDS NIH HHS · R01 NS039837 · United States
NINDS NIH HHS · NS39837 · United States
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