Long-term depression of NMDA receptor-mediated synaptic transmission is dependent on activation of metabotropic glutamate receptors and is altered to long-term potentiation by low intracellular calcium buffering.

Content Provider	Semantic Scholar
Author	Anwyl, Roger
Copyright Year	2006
Abstract	Synaptic plasticity of NMDA receptor (NMDAR)-mediated transmission was investigated in the rat dentate gyrus in vitro. Isolated NMDAR EPSCs were recorded from granule cells of the dentate gyrus in response to stimulation of the medial perforant path. Long-term potentiation (LTP) or long-term depression (LTD) of NMDAR EPSCs was observed in response to brief high-frequency stimulation (HFS), with the direction and extent of plasticity dependent on the concentration and type (EGTA vs BAPTA) of the intracellular Ca2+ buffer. LTD was induced in higher concentrations of EGTA and BAPTA than LTP, and BAPTA was approximately 100-fold more potent than EGTA. Although LTD was induced in a high concentration of EGTA (10 mM), a high concentration of BAPTA (10 mM) blocked both LTP and LTD. LTP of AMPA receptor (AMPAR)-EPSCs exhibited a lower dependency on Ca2+ buffering than LTP of NMDAR EPSCs, because LTP of AMPAR EPSCs was induced by HFS in high EGTA (10 mM). We also identified a role for metabotropic glutamate receptor 5 (mGluR5) in NMDAR plasticity. HFS LTD was blocked by the group I/II mGluR antagonist LY341495 ((2S)-2-amino-2-[(1S, 2S)-2-carboxycycloprop-1-yl]-3(xanth-9-yl)propanoic acid) and by the mGluR5-selective antagonist 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP). Similarly, low-frequency stimulation-induced LTD of NMDAR EPSCs was also blocked by MPEP. These findings suggest that the direction of plasticity of NMDARs is determined by the intracellular free Ca2+ concentration and is dependent on activation of mGluR5.
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Alternate Webpage(s)	http://www.jneurosci.org/content/jneuro/26/4/1128.full.pdf
PubMed reference number	16436598v1
Volume Number	26
Issue Number	4
Journal	The Journal of neuroscience : the official journal of the Society for Neuroscience
Language	English
Access Restriction	Open
Subject Keyword	AMPA Receptors Anti-N-Methyl-D-Aspartate Receptor Encephalitis Buffers Calcium ion Depressive disorder Egtazic Acid Glutamic Acid Hyalinosis, Systemic In Vitro [Publication Type] LY 341495 Long-Term Potentiation N-Methyl-D-Aspartate Receptors N-Methylaspartate Perforant Pathway Receptors, Metabotropic Glutamate Structure of dentate gyrus Synaptic Transmission chemosensitization/potentiation emotional dependency metabotropic glutamate receptor 5
Content Type	Text
Resource Type	Article