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Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression Bartlett, Thomas E; Lu, Jie; Wang, Yu T

Abstract

Background: The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices. Results We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1. Conclusions These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature.

Item Metadata

Title
Slice orientation and muscarinic acetylcholine receptor activation determine the involvement of N-methyl D-aspartate receptor subunit GluN2B in hippocampal area CA1 long-term depression
Creator
Bartlett, Thomas E; Lu, Jie; Wang, Yu T
Contributor
University of British Columbia. Djavad Mowafaghian Centre for Brain Health
Publisher
BioMed Central
Date Issued
2011-11-15
Description
Background: The contribution of different GluN2 subunits of the N-methyl D-aspartate (NMDA) receptor to the induction of bidirectional hippocampal synaptic plasticity is a controversial topic. As both supporting and refuting evidence for the hypothesis of subunit specialization in opposing directions of plasticity has accumulated since it was first proposed a few years ago, we hypothesize that differences in experimental conditions may have in part contributed to some of the inconsistent results from these studies. Here we investigate the controversial hypothesis that long-term depression (LTD) is preferentially induced by GluN2B-containing NMDA receptors in area CA1 of hippocampal slices. Results We find that brain slices from 2-3 week old rats prepared in the sagittal orientation have GluN2B-independent LTD whereas slices prepared in the coronal orientation have GluN2B-dependent LTD. There was no difference between the orientations in the fraction of the NMDAR EPSC sensitive to a GluN2B-selective antagonist, leading us to believe that the intracellular signaling properties of the NMDARs were different in the two preparations. Coronal slices had greater association of LTD-related intracellular signaling protein RasGRF1 with GluN2B relative to sagittal slices. Antagonism of muscarinic acetylcholine receptors (mAChRs) in the sagittal slices returned LTD to a GluN2B-dependent form and increased the association of GluN2B with RasGRF1. Conclusions These results suggest a novel form of NMDAR modulation by mAChRs and clarify some disagreement in the literature.
Subject
Hippocampus; Long-term depression; N-methyl; D-Aspartate receptor; muscarinic acetylcholine receptor
Genre
Article
Type
Text
Language
eng
Date Available
2015-11-18
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0216451
URI
http://hdl.handle.net/2429/55382
Affiliation
Medicine, Faculty of
Citation
Molecular Brain. 2011 Nov 15;4(1):41
Publisher DOI
10.1186/1756-6606-4-41
Peer Review Status
Reviewed
Scholarly Level
Faculty
Copyright Holder
Bartlett et al; licensee BioMed Central Ltd.
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)