Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
Identifieur interne : 000671 ( Pmc/Curation ); précédent : 000670; suivant : 000672Limiting glutamate transmission in a Vglut2-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion
Auteurs : Nadine Schweizer [Suède] ; Stéfano Pupe [Suède, Brésil] ; Emma Arvidsson [Suède] ; Karin Nordenankar [Suède] ; Casey J. A. Smith-Anttila [Suède] ; Souha Mahmoudi [Canada] ; Anna Andrén [Suède] ; Sylvie Dumas [France] ; Aparna Rajagopalan [Suède] ; Daniel Lévesque [Canada] ; Richardson N. Leão [Suède, Brésil] ; Sa Wallén-Mackenzie [Suède]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
Abstract
The subthalamic nucleus (STN) has an important role in locomotion, as evidenced by the successful use of high-frequency stimulation of this structure as treatment for Parkinson disease. There is considerable uncertainty, however, regarding the mechanism through which this effect is achieved. We identified a promoter diversity within this nucleus and observed a movement phenotype displayed as decreased latency in initiation of movement and increased locomotion in both horizontal and vertical planes as a consequence of blunting, but not eliminating, expression of
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DOI: 10.1073/pnas.1323499111
PubMed: 24821804
PubMed Central: 4040590
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Limiting glutamate transmission in a <italic>Vglut2</italic>-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion</title><author><name sortKey="Schweizer, Nadine" sort="Schweizer, Nadine" uniqKey="Schweizer N" first="Nadine" last="Schweizer">Nadine Schweizer</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pupe, Stefano" sort="Pupe, Stefano" uniqKey="Pupe S" first="Stéfano" last="Pupe">Stéfano Pupe</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Brain Institute,<institution>Federal University of Rio Grande do Norte</institution>, 2155-59056-450 Natal-RN,<country>Brazil</country>;</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Arvidsson, Emma" sort="Arvidsson, Emma" uniqKey="Arvidsson E" first="Emma" last="Arvidsson">Emma Arvidsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nordenankar, Karin" sort="Nordenankar, Karin" uniqKey="Nordenankar K" first="Karin" last="Nordenankar">Karin Nordenankar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith Anttila, Casey J A" sort="Smith Anttila, Casey J A" uniqKey="Smith Anttila C" first="Casey J. A." last="Smith-Anttila">Casey J. A. Smith-Anttila</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mahmoudi, Souha" sort="Mahmoudi, Souha" uniqKey="Mahmoudi S" first="Souha" last="Mahmoudi">Souha Mahmoudi</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff4">Faculty of Pharmacy,<institution>Université de Montréal</institution>, Montréal, QC,<country>Canada</country> H3C 3J7</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Andren, Anna" sort="Andren, Anna" uniqKey="Andren A" first="Anna" last="Andrén">Anna Andrén</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dumas, Sylvie" sort="Dumas, Sylvie" uniqKey="Dumas S" first="Sylvie" last="Dumas">Sylvie Dumas</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Oramacell</institution>, 75006 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rajagopalan, Aparna" sort="Rajagopalan, Aparna" uniqKey="Rajagopalan A" first="Aparna" last="Rajagopalan">Aparna Rajagopalan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, Daniel" sort="Levesque, Daniel" uniqKey="Levesque D" first="Daniel" last="Lévesque">Daniel Lévesque</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff4">Faculty of Pharmacy,<institution>Université de Montréal</institution>, Montréal, QC,<country>Canada</country> H3C 3J7</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Leao, Richardson N" sort="Leao, Richardson N" uniqKey="Leao R" first="Richardson N." last="Leão">Richardson N. Leão</name><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Brain Institute,<institution>Federal University of Rio Grande do Norte</institution>, 2155-59056-450 Natal-RN,<country>Brazil</country>;</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wallen Mackenzie, Sa" sort="Wallen Mackenzie, Sa" uniqKey="Wallen Mackenzie " first=" Sa" last="Wallén-Mackenzie"> Sa Wallén-Mackenzie</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24821804</idno><idno type="pmc">4040590</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040590</idno><idno type="RBID">PMC:4040590</idno><idno type="doi">10.1073/pnas.1323499111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000671</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000671</idno><idno type="wicri:Area/Pmc/Curation">000671</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000671</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Limiting glutamate transmission in a <italic>Vglut2</italic>-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion</title><author><name sortKey="Schweizer, Nadine" sort="Schweizer, Nadine" uniqKey="Schweizer N" first="Nadine" last="Schweizer">Nadine Schweizer</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Pupe, Stefano" sort="Pupe, Stefano" uniqKey="Pupe S" first="Stéfano" last="Pupe">Stéfano Pupe</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Brain Institute,<institution>Federal University of Rio Grande do Norte</institution>, 2155-59056-450 Natal-RN,<country>Brazil</country>;</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Arvidsson, Emma" sort="Arvidsson, Emma" uniqKey="Arvidsson E" first="Emma" last="Arvidsson">Emma Arvidsson</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Nordenankar, Karin" sort="Nordenankar, Karin" uniqKey="Nordenankar K" first="Karin" last="Nordenankar">Karin Nordenankar</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Smith Anttila, Casey J A" sort="Smith Anttila, Casey J A" uniqKey="Smith Anttila C" first="Casey J. A." last="Smith-Anttila">Casey J. A. Smith-Anttila</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mahmoudi, Souha" sort="Mahmoudi, Souha" uniqKey="Mahmoudi S" first="Souha" last="Mahmoudi">Souha Mahmoudi</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff4">Faculty of Pharmacy,<institution>Université de Montréal</institution>, Montréal, QC,<country>Canada</country> H3C 3J7</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Andren, Anna" sort="Andren, Anna" uniqKey="Andren A" first="Anna" last="Andrén">Anna Andrén</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Dumas, Sylvie" sort="Dumas, Sylvie" uniqKey="Dumas S" first="Sylvie" last="Dumas">Sylvie Dumas</name><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Oramacell</institution>, 75006 Paris,<country>France</country></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rajagopalan, Aparna" sort="Rajagopalan, Aparna" uniqKey="Rajagopalan A" first="Aparna" last="Rajagopalan">Aparna Rajagopalan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Levesque, Daniel" sort="Levesque, Daniel" uniqKey="Levesque D" first="Daniel" last="Lévesque">Daniel Lévesque</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff4">Faculty of Pharmacy,<institution>Université de Montréal</institution>, Montréal, QC,<country>Canada</country> H3C 3J7</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Leao, Richardson N" sort="Leao, Richardson N" uniqKey="Leao R" first="Richardson N." last="Leão">Richardson N. Leão</name><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Brain Institute,<institution>Federal University of Rio Grande do Norte</institution>, 2155-59056-450 Natal-RN,<country>Brazil</country>;</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Wallen Mackenzie, Sa" sort="Wallen Mackenzie, Sa" uniqKey="Wallen Mackenzie " first=" Sa" last="Wallén-Mackenzie"> Sa Wallén-Mackenzie</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2">Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>The subthalamic nucleus (STN) has an important role in locomotion, as evidenced by the successful use of high-frequency stimulation of this structure as treatment for Parkinson disease. There is considerable uncertainty, however, regarding the mechanism through which this effect is achieved. We identified a promoter diversity within this nucleus and observed a movement phenotype displayed as decreased latency in initiation of movement and increased locomotion in both horizontal and vertical planes as a consequence of blunting, but not eliminating, expression of <italic>Vglut2</italic> in the STN of mice. In contrast to various lesion and high-frequency-stimulation studies of the STN, our genetic approach leaves cognitive functions intact. Taken together, our findings could be important for advancing future therapeutic strategies.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="iso-abbrev">Proc. Natl. Acad. Sci. U.S.A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24821804</article-id><article-id pub-id-type="pmc">4040590</article-id><article-id pub-id-type="publisher-id">201323499</article-id><article-id pub-id-type="doi">10.1073/pnas.1323499111</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Neuroscience</subject></subj-group></subj-group></article-categories><title-group><article-title>Limiting glutamate transmission in a <italic>Vglut2</italic>-expressing subpopulation of the subthalamic nucleus is sufficient to cause hyperlocomotion</article-title><alt-title alt-title-type="short"><italic>Vglut2</italic> in the STN</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Schweizer</surname><given-names>Nadine</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Pupe</surname><given-names>Stéfano</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref><xref ref-type="author-notes" rid="fn2"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Arvidsson</surname><given-names>Emma</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nordenankar</surname><given-names>Karin</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Smith-Anttila</surname><given-names>Casey J. A.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mahmoudi</surname><given-names>Souha</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Andrén</surname><given-names>Anna</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Dumas</surname><given-names>Sylvie</given-names></name><xref ref-type="aff" rid="aff5"><sup>e</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rajagopalan</surname><given-names>Aparna</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lévesque</surname><given-names>Daniel</given-names></name><xref ref-type="aff" rid="aff4"><sup>d</sup></xref></contrib><contrib contrib-type="author"><name><surname>Leão</surname><given-names>Richardson N.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wallén-Mackenzie</surname><given-names>Åsa</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="aff" rid="aff2"><sup>b</sup></xref><xref ref-type="corresp" rid="cor1"><sup>2</sup></xref></contrib><aff id="aff1">Units of<sup>a</sup>Functional Neurobiology and</aff><aff id="aff2"><sup>b</sup>Developmental Genetics, Department of Neuroscience, Biomedical Center,<institution>Uppsala University</institution>, S-751 24 Uppsala,<country>Sweden</country>;</aff><aff id="aff3"><sup>c</sup>Brain Institute,<institution>Federal University of Rio Grande do Norte</institution>, 2155-59056-450 Natal-RN,<country>Brazil</country>;</aff><aff id="aff4"><sup>d</sup>Faculty of Pharmacy,<institution>Université de Montréal</institution>, Montréal, QC,<country>Canada</country> H3C 3J7; and</aff><aff id="aff5"><sup>e</sup><institution>Oramacell</institution>, 75006 Paris,<country>France</country></aff></contrib-group><author-notes><corresp id="cor1"><sup>2</sup>To whom correspondence should be addressed. E-mail: <email>asa.mackenzie@neuro.uu.se</email>.</corresp><fn fn-type="edited-by"><p>Edited<xref ref-type="fn" rid="fn1">*</xref> by Tomas G. M. Hokfelt, Karolinska Institutet, Stockholm, Sweden, and approved April 18, 2014 (received for review December 17, 2013)</p></fn><fn fn-type="con"><p>Author contributions: N.S., S.P., S.D., D.L., R.N.L., and Å.W.-M. designed research; N.S., E.A., K.N., C.J.A.S.-A., S.M., A.A., S.D., A.R., D.L., R.N.L., and Å.W.-M. performed research; N.S., S.P., E.A., K.N., C.J.A.S.-A., S.D., D.L., R.N.L., and Å.W.-M. analyzed data; and N.S., S.P., and Å.W.-M. wrote the paper.</p></fn><fn fn-type="equal" id="fn2"><p><sup>1</sup>N.S. and S.P. contributed equally to this work.</p></fn></author-notes><pub-date pub-type="ppub"><day>27</day><month>5</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>12</day><month>5</month><year>2014</year></pub-date><volume>111</volume><issue>21</issue><fpage>7837</fpage><lpage>7842</lpage><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201323499.pdf"></self-uri><abstract abstract-type="executive-summary"><title>Significance</title><p>The subthalamic nucleus (STN) has an important role in locomotion, as evidenced by the successful use of high-frequency stimulation of this structure as treatment for Parkinson disease. There is considerable uncertainty, however, regarding the mechanism through which this effect is achieved. We identified a promoter diversity within this nucleus and observed a movement phenotype displayed as decreased latency in initiation of movement and increased locomotion in both horizontal and vertical planes as a consequence of blunting, but not eliminating, expression of <italic>Vglut2</italic> in the STN of mice. In contrast to various lesion and high-frequency-stimulation studies of the STN, our genetic approach leaves cognitive functions intact. Taken together, our findings could be important for advancing future therapeutic strategies.</p></abstract><abstract><p>The subthalamic nucleus (STN) is a key area of the basal ganglia circuitry regulating movement. We identified a subpopulation of neurons within this structure that coexpresses <italic>Vglut2</italic> and <italic>Pitx2</italic>, and by conditional targeting of this subpopulation we reduced <italic>Vglut2</italic> expression levels in the STN by 40%, leaving <italic>Pitx2</italic> expression intact. This reduction diminished, yet did not eliminate, glutamatergic transmission in the substantia nigra pars reticulata and entopeduncular nucleus, two major targets of the STN. The knockout mice displayed hyperlocomotion and decreased latency in the initiation of movement while preserving normal gait and balance. Spatial cognition, social function, and level of impulsive choice also remained undisturbed. Furthermore, these mice showed reduced dopamine transporter binding and slower dopamine clearance in vivo, suggesting that <italic>Vglut2</italic>-expressing cells in the STN regulate dopaminergic transmission. Our results demonstrate that altering the contribution of a limited population within the STN is sufficient to achieve results similar to STN lesions and high-frequency stimulation, but with fewer side effects.</p></abstract><kwd-group><kwd>Parkinson disease</kwd><kwd>deep brain stimulation</kwd><kwd>vesicular transporter</kwd><kwd>optogenetics</kwd><kwd>striatum</kwd></kwd-group><counts><page-count count="6"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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