Activity-dependent site-specific changes of glutamate receptor composition in vivo
The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs i...
Gespeichert in:
Veröffentlicht in: | Nature neuroscience 2008-06, Vol.11 (6), p.659-666 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 666 |
---|---|
container_issue | 6 |
container_start_page | 659 |
container_title | Nature neuroscience |
container_volume | 11 |
creator | Schmid, Andreas Hallermann, Stefan Kittel, Robert J Khorramshahi, Omid Frölich, Andreas M J Quentin, Christine Rasse, Tobias M Mertel, Sara Heckmann, Manfred Sigrist, Stephan J |
description | The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs
in vivo
during the formation of new postsynaptic densities (PSDs) at
Drosophila
neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly. |
doi_str_mv | 10.1038/nn.2122 |
format | Article |
fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_864951584</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A186823027</galeid><sourcerecordid>A186823027</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-2078a9fd8f9af64548fa6f8270f34f152bae7fb302264715bb30a474046a78403</originalsourceid><addsrcrecordid>eNqFkl9rFDEUxYMotlbxG8jgQ7UPsybZ_JvHpdhaKAhVn0M2c7OmzCRjklnst2-WXSjtQ0seckl-53JPchD6SPCC4KX6FsKCEkpfoWPCmWiJpOJ1rXEnW0G5OELvcr7FGEuuurfoiCgmOkXwMbpZ2eK3vty1PUwQegilyb5Amyew3nnb2L8mbCA30TWbYS5mNAWaBBamElNj4zjFKvAxND40W7-N79EbZ4YMHw77Cfpz8f33-Y_2-ufl1fnqurVM8tJSLJXpXK9cZ5xgnClnhFNUYrdkjnC6NiDdeokpFUwSvq6lYZJhJoxUDC9P0Jd93ynFfzPkokefLQyDCRDnrJVgHSdcsUqePktKLIUkhL4IUtxh1klVwc9PwNs4p1DtaioZx7y-fIUWe2hjBtA-uFiSsXX1MHobAzhfz1dECUWrzZ3g7JGgMgX-l42Zc9ZXv24eswf3NsWcEzg9JT-adKcJ1rtM6BD0LhOV_HSYdV6P0D9whxBU4OseyPWq_nV6MPO01z3SirwY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>274505097</pqid></control><display><type>article</type><title>Activity-dependent site-specific changes of glutamate receptor composition in vivo</title><source>MEDLINE</source><source>SpringerLink Journals</source><source>Nature Journals Online</source><creator>Schmid, Andreas ; Hallermann, Stefan ; Kittel, Robert J ; Khorramshahi, Omid ; Frölich, Andreas M J ; Quentin, Christine ; Rasse, Tobias M ; Mertel, Sara ; Heckmann, Manfred ; Sigrist, Stephan J</creator><creatorcontrib>Schmid, Andreas ; Hallermann, Stefan ; Kittel, Robert J ; Khorramshahi, Omid ; Frölich, Andreas M J ; Quentin, Christine ; Rasse, Tobias M ; Mertel, Sara ; Heckmann, Manfred ; Sigrist, Stephan J</creatorcontrib><description>The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs
in vivo
during the formation of new postsynaptic densities (PSDs) at
Drosophila
neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly.</description><identifier>ISSN: 1097-6256</identifier><identifier>EISSN: 1546-1726</identifier><identifier>DOI: 10.1038/nn.2122</identifier><identifier>PMID: 18469810</identifier><identifier>CODEN: NANEFN</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animal Genetics and Genomics ; Animals ; Animals, Genetically Modified ; Behavioral Sciences ; Biological Techniques ; Biomedical and Life Sciences ; Biomedicine ; Computer Simulation ; Drosophila ; Drosophila Proteins ; Excitatory Postsynaptic Potentials - physiology ; Excitatory Postsynaptic Potentials - radiation effects ; Fluorescence Recovery After Photobleaching - methods ; Gene Expression Regulation - physiology ; Glutamate ; Glutamic Acid - metabolism ; Green Fluorescent Proteins - metabolism ; Insects ; Metabotropic glutamate receptors ; Models, Biological ; Mutation - physiology ; Neurobiology ; Neuromuscular Junction - metabolism ; Neurosciences ; Patch-Clamp Techniques ; Properties ; Protein Transport - physiology ; Receptors, AMPA - genetics ; Receptors, AMPA - physiology ; Time Factors</subject><ispartof>Nature neuroscience, 2008-06, Vol.11 (6), p.659-666</ispartof><rights>Springer Nature America, Inc. 2008</rights><rights>COPYRIGHT 2008 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jun 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-2078a9fd8f9af64548fa6f8270f34f152bae7fb302264715bb30a474046a78403</citedby><cites>FETCH-LOGICAL-c475t-2078a9fd8f9af64548fa6f8270f34f152bae7fb302264715bb30a474046a78403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nn.2122$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nn.2122$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18469810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schmid, Andreas</creatorcontrib><creatorcontrib>Hallermann, Stefan</creatorcontrib><creatorcontrib>Kittel, Robert J</creatorcontrib><creatorcontrib>Khorramshahi, Omid</creatorcontrib><creatorcontrib>Frölich, Andreas M J</creatorcontrib><creatorcontrib>Quentin, Christine</creatorcontrib><creatorcontrib>Rasse, Tobias M</creatorcontrib><creatorcontrib>Mertel, Sara</creatorcontrib><creatorcontrib>Heckmann, Manfred</creatorcontrib><creatorcontrib>Sigrist, Stephan J</creatorcontrib><title>Activity-dependent site-specific changes of glutamate receptor composition in vivo</title><title>Nature neuroscience</title><addtitle>Nat Neurosci</addtitle><addtitle>Nat Neurosci</addtitle><description>The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs
in vivo
during the formation of new postsynaptic densities (PSDs) at
Drosophila
neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly.</description><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>Behavioral Sciences</subject><subject>Biological Techniques</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Computer Simulation</subject><subject>Drosophila</subject><subject>Drosophila Proteins</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Excitatory Postsynaptic Potentials - radiation effects</subject><subject>Fluorescence Recovery After Photobleaching - methods</subject><subject>Gene Expression Regulation - physiology</subject><subject>Glutamate</subject><subject>Glutamic Acid - metabolism</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Insects</subject><subject>Metabotropic glutamate receptors</subject><subject>Models, Biological</subject><subject>Mutation - physiology</subject><subject>Neurobiology</subject><subject>Neuromuscular Junction - metabolism</subject><subject>Neurosciences</subject><subject>Patch-Clamp Techniques</subject><subject>Properties</subject><subject>Protein Transport - physiology</subject><subject>Receptors, AMPA - genetics</subject><subject>Receptors, AMPA - physiology</subject><subject>Time Factors</subject><issn>1097-6256</issn><issn>1546-1726</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkl9rFDEUxYMotlbxG8jgQ7UPsybZ_JvHpdhaKAhVn0M2c7OmzCRjklnst2-WXSjtQ0seckl-53JPchD6SPCC4KX6FsKCEkpfoWPCmWiJpOJ1rXEnW0G5OELvcr7FGEuuurfoiCgmOkXwMbpZ2eK3vty1PUwQegilyb5Amyew3nnb2L8mbCA30TWbYS5mNAWaBBamElNj4zjFKvAxND40W7-N79EbZ4YMHw77Cfpz8f33-Y_2-ufl1fnqurVM8tJSLJXpXK9cZ5xgnClnhFNUYrdkjnC6NiDdeokpFUwSvq6lYZJhJoxUDC9P0Jd93ynFfzPkokefLQyDCRDnrJVgHSdcsUqePktKLIUkhL4IUtxh1klVwc9PwNs4p1DtaioZx7y-fIUWe2hjBtA-uFiSsXX1MHobAzhfz1dECUWrzZ3g7JGgMgX-l42Zc9ZXv24eswf3NsWcEzg9JT-adKcJ1rtM6BD0LhOV_HSYdV6P0D9whxBU4OseyPWq_nV6MPO01z3SirwY</recordid><startdate>20080601</startdate><enddate>20080601</enddate><creator>Schmid, Andreas</creator><creator>Hallermann, Stefan</creator><creator>Kittel, Robert J</creator><creator>Khorramshahi, Omid</creator><creator>Frölich, Andreas M J</creator><creator>Quentin, Christine</creator><creator>Rasse, Tobias M</creator><creator>Mertel, Sara</creator><creator>Heckmann, Manfred</creator><creator>Sigrist, Stephan J</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>RC3</scope><scope>7SS</scope><scope>7X8</scope></search><sort><creationdate>20080601</creationdate><title>Activity-dependent site-specific changes of glutamate receptor composition in vivo</title><author>Schmid, Andreas ; Hallermann, Stefan ; Kittel, Robert J ; Khorramshahi, Omid ; Frölich, Andreas M J ; Quentin, Christine ; Rasse, Tobias M ; Mertel, Sara ; Heckmann, Manfred ; Sigrist, Stephan J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-2078a9fd8f9af64548fa6f8270f34f152bae7fb302264715bb30a474046a78403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animal Genetics and Genomics</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>Behavioral Sciences</topic><topic>Biological Techniques</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Computer Simulation</topic><topic>Drosophila</topic><topic>Drosophila Proteins</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Excitatory Postsynaptic Potentials - radiation effects</topic><topic>Fluorescence Recovery After Photobleaching - methods</topic><topic>Gene Expression Regulation - physiology</topic><topic>Glutamate</topic><topic>Glutamic Acid - metabolism</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Insects</topic><topic>Metabotropic glutamate receptors</topic><topic>Models, Biological</topic><topic>Mutation - physiology</topic><topic>Neurobiology</topic><topic>Neuromuscular Junction - metabolism</topic><topic>Neurosciences</topic><topic>Patch-Clamp Techniques</topic><topic>Properties</topic><topic>Protein Transport - physiology</topic><topic>Receptors, AMPA - genetics</topic><topic>Receptors, AMPA - physiology</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schmid, Andreas</creatorcontrib><creatorcontrib>Hallermann, Stefan</creatorcontrib><creatorcontrib>Kittel, Robert J</creatorcontrib><creatorcontrib>Khorramshahi, Omid</creatorcontrib><creatorcontrib>Frölich, Andreas M J</creatorcontrib><creatorcontrib>Quentin, Christine</creatorcontrib><creatorcontrib>Rasse, Tobias M</creatorcontrib><creatorcontrib>Mertel, Sara</creatorcontrib><creatorcontrib>Heckmann, Manfred</creatorcontrib><creatorcontrib>Sigrist, Stephan J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest One Psychology</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>MEDLINE - Academic</collection><jtitle>Nature neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schmid, Andreas</au><au>Hallermann, Stefan</au><au>Kittel, Robert J</au><au>Khorramshahi, Omid</au><au>Frölich, Andreas M J</au><au>Quentin, Christine</au><au>Rasse, Tobias M</au><au>Mertel, Sara</au><au>Heckmann, Manfred</au><au>Sigrist, Stephan J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activity-dependent site-specific changes of glutamate receptor composition in vivo</atitle><jtitle>Nature neuroscience</jtitle><stitle>Nat Neurosci</stitle><addtitle>Nat Neurosci</addtitle><date>2008-06-01</date><risdate>2008</risdate><volume>11</volume><issue>6</issue><spage>659</spage><epage>666</epage><pages>659-666</pages><issn>1097-6256</issn><eissn>1546-1726</eissn><coden>NANEFN</coden><abstract>The subunit composition of postsynaptic non–NMDA-type glutamate receptors (GluRs) determines the function and trafficking of the receptor. Changes in GluR composition have been implicated in the homeostasis of neuronal excitability and synaptic plasticity underlying learning. Here, we imaged GluRs
in vivo
during the formation of new postsynaptic densities (PSDs) at
Drosophila
neuromuscular junctions coexpressing GluRIIA and GluRIIB subunits. GluR composition was independently regulated at directly neighboring PSDs on a submicron scale. Immature PSDs typically had large amounts of GluRIIA and small amounts of GluRIIB. During subsequent PSD maturation, however, the GluRIIA/GluRIIB composition changed and became more balanced. Reducing presynaptic glutamate release increased GluRIIA, but decreased GluRIIB incorporation. Moreover, the maturation of GluR composition correlated in a site-specific manner with the level of Bruchpilot, an active zone protein that is essential for mature glutamate release. Thus, we show that an activity-dependent, site-specific control of GluR composition can contribute to match pre- and postsynaptic assembly.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>18469810</pmid><doi>10.1038/nn.2122</doi><tpages>8</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1097-6256 |
ispartof | Nature neuroscience, 2008-06, Vol.11 (6), p.659-666 |
issn | 1097-6256 1546-1726 |
language | eng |
recordid | cdi_proquest_miscellaneous_864951584 |
source | MEDLINE; SpringerLink Journals; Nature Journals Online |
subjects | Animal Genetics and Genomics Animals Animals, Genetically Modified Behavioral Sciences Biological Techniques Biomedical and Life Sciences Biomedicine Computer Simulation Drosophila Drosophila Proteins Excitatory Postsynaptic Potentials - physiology Excitatory Postsynaptic Potentials - radiation effects Fluorescence Recovery After Photobleaching - methods Gene Expression Regulation - physiology Glutamate Glutamic Acid - metabolism Green Fluorescent Proteins - metabolism Insects Metabotropic glutamate receptors Models, Biological Mutation - physiology Neurobiology Neuromuscular Junction - metabolism Neurosciences Patch-Clamp Techniques Properties Protein Transport - physiology Receptors, AMPA - genetics Receptors, AMPA - physiology Time Factors |
title | Activity-dependent site-specific changes of glutamate receptor composition in vivo |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T14%3A21%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activity-dependent%20site-specific%20changes%20of%20glutamate%20receptor%20composition%20in%20vivo&rft.jtitle=Nature%20neuroscience&rft.au=Schmid,%20Andreas&rft.date=2008-06-01&rft.volume=11&rft.issue=6&rft.spage=659&rft.epage=666&rft.pages=659-666&rft.issn=1097-6256&rft.eissn=1546-1726&rft.coden=NANEFN&rft_id=info:doi/10.1038/nn.2122&rft_dat=%3Cgale_proqu%3EA186823027%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=274505097&rft_id=info:pmid/18469810&rft_galeid=A186823027&rfr_iscdi=true |