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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">NORADRENERGIC CONTROL OF CORTICO-STRIATO-THALAMIC AND MESOLIMBIC CROSS-STRUCTURAL SYNCHRONY</title><author><name sortKey="Dzirasa, Kafui" sort="Dzirasa, Kafui" uniqKey="Dzirasa K" first="Kafui" last="Dzirasa">Kafui Dzirasa</name><affiliation><nlm:aff id="A1"> Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A5"> Center for Neuroengineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Phillips, H Westley" sort="Phillips, H Westley" uniqKey="Phillips H" first="H. Westley" last="Phillips">H. Westley Phillips</name><affiliation><nlm:aff id="A2"> Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Sotnikova, Tatyana D" sort="Sotnikova, Tatyana D" uniqKey="Sotnikova T" first="Tatyana D." last="Sotnikova">Tatyana D. Sotnikova</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy</nlm:aff></affiliation></author><author><name sortKey="Salahpour, Ali" sort="Salahpour, Ali" uniqKey="Salahpour A" first="Ali" last="Salahpour">Ali Salahpour</name><affiliation><nlm:aff id="A8"> Dept. of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada M5S 1A8</nlm:aff></affiliation></author><author><name sortKey="Kumar, Sunil" sort="Kumar, Sunil" uniqKey="Kumar S" first="Sunil" last="Kumar">Sunil Kumar</name><affiliation><nlm:aff id="A1"> Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Gainetdinov, Raul R" sort="Gainetdinov, Raul R" uniqKey="Gainetdinov R" first="Raul R." last="Gainetdinov">Raul R. Gainetdinov</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy</nlm:aff></affiliation></author><author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Nicolelis, Miguel A L" sort="Nicolelis, Miguel A L" uniqKey="Nicolelis M" first="Miguel A. L." last="Nicolelis">Miguel A. L. Nicolelis</name><affiliation><nlm:aff id="A2"> Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A4"> Dept. of Psychology and Neuroscience, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A5"> Center for Neuroengineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A6"> Dept. of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A9"> Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal, Brazil</nlm:aff></affiliation><affiliation><nlm:aff id="A10"> Blaise Pascal International Research Chair, École Supérieure de Physique et de Chimie Industrielles, Paris, France</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20445065</idno><idno type="pmc">2988440</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988440</idno><idno type="RBID">PMC:2988440</idno><idno type="doi">10.1523/JNEUROSCI.0764-10.2010</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000422</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000422</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NORADRENERGIC CONTROL OF CORTICO-STRIATO-THALAMIC AND MESOLIMBIC CROSS-STRUCTURAL SYNCHRONY</title><author><name sortKey="Dzirasa, Kafui" sort="Dzirasa, Kafui" uniqKey="Dzirasa K" first="Kafui" last="Dzirasa">Kafui Dzirasa</name><affiliation><nlm:aff id="A1"> Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A5"> Center for Neuroengineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Phillips, H Westley" sort="Phillips, H Westley" uniqKey="Phillips H" first="H. Westley" last="Phillips">H. Westley Phillips</name><affiliation><nlm:aff id="A2"> Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Sotnikova, Tatyana D" sort="Sotnikova, Tatyana D" uniqKey="Sotnikova T" first="Tatyana D." last="Sotnikova">Tatyana D. Sotnikova</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy</nlm:aff></affiliation></author><author><name sortKey="Salahpour, Ali" sort="Salahpour, Ali" uniqKey="Salahpour A" first="Ali" last="Salahpour">Ali Salahpour</name><affiliation><nlm:aff id="A8"> Dept. of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada M5S 1A8</nlm:aff></affiliation></author><author><name sortKey="Kumar, Sunil" sort="Kumar, Sunil" uniqKey="Kumar S" first="Sunil" last="Kumar">Sunil Kumar</name><affiliation><nlm:aff id="A1"> Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Gainetdinov, Raul R" sort="Gainetdinov, Raul R" uniqKey="Gainetdinov R" first="Raul R." last="Gainetdinov">Raul R. Gainetdinov</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A7"> Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy</nlm:aff></affiliation></author><author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name><affiliation><nlm:aff id="A3"> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation></author><author><name sortKey="Nicolelis, Miguel A L" sort="Nicolelis, Miguel A L" uniqKey="Nicolelis M" first="Miguel A. L." last="Nicolelis">Miguel A. L. Nicolelis</name><affiliation><nlm:aff id="A2"> Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A4"> Dept. of Psychology and Neuroscience, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A5"> Center for Neuroengineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A6"> Dept. of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710</nlm:aff></affiliation><affiliation><nlm:aff id="A9"> Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal, Brazil</nlm:aff></affiliation><affiliation><nlm:aff id="A10"> Blaise Pascal International Research Chair, École Supérieure de Physique et de Chimie Industrielles, Paris, France</nlm:aff></affiliation></author></analytic><series><title level="j">The Journal of neuroscience : the official journal of the Society for Neuroscience</title><idno type="ISSN">0270-6474</idno><idno type="eISSN">1529-2401</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">While normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials (LFPs) and single neuron activity across ten interconnected brain areas (ventral striatum, frontal association cortex hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits, and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute twelve-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-DOPA 100mg/kg or L-DOPS 5mg/kg), or a selective serotonin reuptake inhibitor (fluoxetine 20mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striatal-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8102140</journal-id><journal-id journal-id-type="pubmed-jr-id">5035</journal-id><journal-id journal-id-type="nlm-ta">J Neurosci</journal-id><journal-title>The Journal of neuroscience : the official journal of the Society for Neuroscience</journal-title><issn pub-type="ppub">0270-6474</issn><issn pub-type="epub">1529-2401</issn></journal-meta><article-meta><article-id pub-id-type="pmid">20445065</article-id><article-id pub-id-type="pmc">2988440</article-id><article-id pub-id-type="doi">10.1523/JNEUROSCI.0764-10.2010</article-id><article-id pub-id-type="manuscript">NIHMS197415</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>NORADRENERGIC CONTROL OF CORTICO-STRIATO-THALAMIC AND MESOLIMBIC CROSS-STRUCTURAL SYNCHRONY</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Dzirasa</surname><given-names>Kafui</given-names></name><xref rid="A1" ref-type="aff">1</xref><xref rid="A5" ref-type="aff">5</xref><xref rid="FN1" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Phillips</surname><given-names>H. Westley</given-names></name><xref rid="A2" ref-type="aff">2</xref></contrib><contrib contrib-type="author"><name><surname>Sotnikova</surname><given-names>Tatyana D.</given-names></name><xref rid="A3" ref-type="aff">3</xref><xref rid="A7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Salahpour</surname><given-names>Ali</given-names></name><xref rid="A8" ref-type="aff">8</xref></contrib><contrib contrib-type="author"><name><surname>Kumar</surname><given-names>Sunil</given-names></name><xref rid="A1" ref-type="aff">1</xref></contrib><contrib contrib-type="author"><name><surname>Gainetdinov</surname><given-names>Raul R.</given-names></name><xref rid="A3" ref-type="aff">3</xref><xref rid="A7" ref-type="aff">7</xref></contrib><contrib contrib-type="author"><name><surname>Caron</surname><given-names>Marc G.</given-names></name><xref rid="A3" ref-type="aff">3</xref></contrib><contrib contrib-type="author"><name><surname>Nicolelis</surname><given-names>Miguel A. L.</given-names></name><xref rid="A2" ref-type="aff">2</xref><xref rid="A4" ref-type="aff">4</xref><xref rid="A5" ref-type="aff">5</xref><xref rid="A6" ref-type="aff">6</xref><xref rid="A9" ref-type="aff">9</xref><xref rid="A10" ref-type="aff">10</xref></contrib></contrib-group><aff id="A1"><label>1</label> Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A2"><label>2</label> Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A3"><label>3</label> Dept. of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A4"><label>4</label> Dept. of Psychology and Neuroscience, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A5"><label>5</label> Center for Neuroengineering, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A6"><label>6</label> Dept. of Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27710</aff><aff id="A7"><label>7</label> Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy</aff><aff id="A8"><label>8</label> Dept. of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada M5S 1A8</aff><aff id="A9"><label>9</label> Edmond and Lily Safra International Institute of Neuroscience of Natal (ELS-IINN), Natal, Brazil</aff><aff id="A10"><label>10</label> Blaise Pascal International Research Chair, École Supérieure de Physique et de Chimie Industrielles, Paris, France</aff><author-notes><corresp id="FN1"><label>*</label>Corresponding Author: Kafui Dzirasa, M.D. Ph.D. (<email>dzira001@mc.duke.edu</email>), Department of Psychiatry and Behavioral Sciences, Center for Neuroengineering, Duke University Medical Center, 333 Bryan Research Building, Durham, NC 27710, USA</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>26</day><month>4</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>5</day><month>5</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>5</day><month>5</month><year>2011</year></pub-date><volume>30</volume><issue>18</issue><fpage>6387</fpage><lpage>6397</lpage><abstract><p id="P1">While normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials (LFPs) and single neuron activity across ten interconnected brain areas (ventral striatum, frontal association cortex hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits, and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute twelve-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-DOPA 100mg/kg or L-DOPS 5mg/kg), or a selective serotonin reuptake inhibitor (fluoxetine 20mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striatal-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.</p></abstract><kwd-group><kwd>Norepinephrine</kwd><kwd>Orbital frontal</kwd><kwd>Striatum</kwd><kwd>VTA</kwd><kwd>Coherence</kwd><kwd>Grooming</kwd></kwd-group><contract-num rid="NS1">R33 NS049534-05
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