Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats.

Hdl Handle:
http://hdl.handle.net/10675.2/155
Title:
Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats.
Authors:
Wang, Deheng; Cui, Zhenzhong; Zeng, Qingwen; Kuang, Hui; Wang, Lei Phillip; Tsien, Joe Z.; Cao, Xiaohua
Abstract:
One major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.
Citation:
PLoS One. 2009 Oct 19; 4(10):e7486
Issue Date:
19-Oct-2009
URI:
http://hdl.handle.net/10675.2/155
DOI:
10.1371/journal.pone.0007486
PubMed ID:
19838302
PubMed Central ID:
PMC2759522
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
ISSN:
1932-6203
Appears in Collections:
Brain & Behavior Discovery Institute: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Dehengen_US
dc.contributor.authorCui, Zhenzhongen_US
dc.contributor.authorZeng, Qingwenen_US
dc.contributor.authorKuang, Huien_US
dc.contributor.authorWang, Lei Phillipen_US
dc.contributor.authorTsien, Joe Z.en_US
dc.contributor.authorCao, Xiaohuaen_US
dc.date.accessioned2010-09-24T22:09:19Z-
dc.date.available2010-09-24T22:09:19Z-
dc.date.issued2009-10-19en_US
dc.identifier.citationPLoS One. 2009 Oct 19; 4(10):e7486en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid19838302en_US
dc.identifier.doi10.1371/journal.pone.0007486en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/155-
dc.description.abstractOne major theory in learning and memory posits that the NR2B gene is a universal genetic factor that acts as rate-limiting molecule in controlling the optimal NMDA receptor's coincidence-detection property and subsequent learning and memory function across multiple animal species. If so, can memory function be enhanced via transgenic overexpression of NR2B in another species other than the previously reported mouse species? To examine these crucial issues, we generated transgenic rats in which NR2B is overexpressed in the cortex and hippocampus and investigated the role of NR2B gene in NMDA receptor-mediated synaptic plasticity and memory functions by combining electrophysiological technique with behavioral measurements. We found that overexpression of the NR2B subunit had no effect on CA1-LTD, but rather resulted in enhanced CA1-LTP and improved memory performances in novel object recognition test, spatial water maze, and delayed-to-nonmatch working memory test. Our slices recordings using NR2A- and NR2B-selective antagonists further demonstrate that the larger LTP in transgenic hippocampal slices was due to contribution from the increased NR2B-containing NMDARs. Therefore, our genetic experiments suggest that NR2B at CA1 synapses is not designated as a rate-limiting factor for the induction of long-term synaptic depression, but rather plays a crucial role in initiating the synaptic potentiation. Moreover, our studies provide strong evidence that the NR2B subunit represents a universal rate-limiting molecule for gating NMDA receptor's optimal coincidence-detection property and for enhancing memory function in adulthood across multiple mammalian species.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCA1 Region, Hippocampal / metabolismen_US
dc.subject.meshFemaleen_US
dc.subject.meshHippocampus / metabolismen_US
dc.subject.meshLong-Term Potentiation / geneticsen_US
dc.subject.meshMaze Learningen_US
dc.subject.meshMemoryen_US
dc.subject.meshNeuronal Plasticityen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Long-Evansen_US
dc.subject.meshRats, Transgenicen_US
dc.subject.meshReceptors, N-Methyl-D-Aspartate / metabolismen_US
dc.subject.meshSynapses / pathologyen_US
dc.subject.meshSynaptic Transmission / geneticsen_US
dc.titleGenetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2759522en_US
dc.contributor.corporatenameBrain & Behavior Discovery Instituteen_US
dc.contributor.corporatenameDepartment of Neurologyen_US

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