Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys
Identifieur interne : 001607 ( Istex/Corpus ); précédent : 001606; suivant : 001608Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys
Auteurs : Carine Karachi ; David Grabli ; Nicolas Baup ; Stéphanie Mounayar ; Dominique Tandé ; Chantal François ; Etienne C. HirschSource :
- Movement Disorders [ 0885-3185 ] ; 2009-06-15.
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Abstract
High‐frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society
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DOI: 10.1002/mds.22547
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The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society</div></front></TEI><istex><corpusName>wiley</corpusName><author><json:item><name>Carine Karachi MD, PhD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string><json:string>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</json:string></affiliations></json:item><json:item><name>David Grabli MD, PhD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string><json:string>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</json:string></affiliations></json:item><json:item><name>Nicolas Baup MD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string><json:string>Department of Psychiatry, Centre Hospitalier Saint‐Anne, Paris, France</json:string></affiliations></json:item><json:item><name>Stéphanie Mounayar PhD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string></affiliations></json:item><json:item><name>Dominique Tandé</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string></affiliations></json:item><json:item><name>Chantal François PhD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string></affiliations></json:item><json:item><name>Etienne C. Hirsch PhD</name><affiliations><json:string>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</json:string><json:string>UPMC Univ Paris 6, UMR_S679, Paris, France</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>monkeys</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>subthalamic nucleus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>microinjections</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>hemiballism</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>stereotypies</value></json:item></subject><language><json:string>eng</json:string></language><abstract>High‐frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. 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type="degree">MD, PhD</roleName></persName><note type="correspondence"><p>Correspondence: INSERM U679, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex 13, France</p></note><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><affiliation>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</affiliation></author><author><persName><forename type="first">David</forename><surname>Grabli</surname><roleName type="degree">MD, PhD</roleName></persName><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><affiliation>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</affiliation></author><author><persName><forename type="first">Nicolas</forename><surname>Baup</surname><roleName 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The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>monkeys</term></item><item><term>subthalamic nucleus</term></item><item><term>microinjections</term></item><item><term>hemiballism</term></item><item><term>stereotypies</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Article category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-10-21">Received</change><change when="2009-02-21">Registration</change><change when="2009-06-15">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><original>false</original><mimetype>text/plain</mimetype><extension>txt</extension><uri>https://api.istex.fr/document/04F55211925A5E8309812187CDE59B3E7A4DBD0F/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1531-8257</doi><issn type="print">0885-3185</issn><issn type="electronic">1531-8257</issn><idGroup><id type="product" value="MDS"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="MOVEMENT DISORDERS">Movement Disorders</title><title type="short">Mov. 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href="file:MDS.MDS22547.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="4"></count><count type="tableTotal" number="2"></count><count type="referenceTotal" number="27"></count><count type="wordTotal" number="6398"></count></countGroup><titleGroup><title type="main" xml:lang="en">Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys<link href="#fn1"></link></title><title type="short" xml:lang="en">Consequences of Subthalamic Nucleus Dysfunction</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1 #af2 #af3" corresponding="yes"><personName><givenNames>Carine</givenNames><familyName>Karachi</familyName><degrees>MD, PhD</degrees></personName><contactDetails><email>carine.karachi@gmail.com</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af1 #af2 #af3"><personName><givenNames>David</givenNames><familyName>Grabli</familyName><degrees>MD, PhD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1 #af2 #af4"><personName><givenNames>Nicolas</givenNames><familyName>Baup</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Stéphanie</givenNames><familyName>Mounayar</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Dominique</givenNames><familyName>Tandé</familyName></personName></creator><creator xml:id="au6" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Chantal</givenNames><familyName>François</familyName><degrees>PhD</degrees></personName></creator><creator xml:id="au7" creatorRole="author" affiliationRef="#af1 #af2"><personName><givenNames>Etienne C.</givenNames><familyName>Hirsch</familyName><degrees>PhD</degrees></personName></creator></creators><affiliationGroup><affiliation xml:id="af1" countryCode="FR" type="organization"><unparsedAffiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="FR" type="organization"><unparsedAffiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="FR" type="organization"><unparsedAffiliation>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="FR" type="organization"><unparsedAffiliation>Department of Psychiatry, Centre Hospitalier Saint‐Anne, Paris, France</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">monkeys</keyword><keyword xml:id="kwd2">subthalamic nucleus</keyword><keyword xml:id="kwd3">microinjections</keyword><keyword xml:id="kwd4">hemiballism</keyword><keyword xml:id="kwd5">stereotypies</keyword></keywordGroup><fundingInfo><fundingAgency>The Tourette Syndrome Association (USA)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Institut National de la Santé et de la Recherche Médicale</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Fondation pour la Recherche Médicale (FRM)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Association Française du Syndrome de Gilles de la Tourette (AFSGT)</fundingAgency></fundingInfo><fundingInfo><fundingAgency>Assistance Publique des Hôpitaux de Paris (APHP)</fundingAgency></fundingInfo><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><p>High‐frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society</p></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Potential conflict of interest: None reported.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><!--Version 0.6 générée le 4-12-2015--><mods version="3.6"><titleInfo lang="en"><title>Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>Consequences of Subthalamic Nucleus Dysfunction</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Dysfunction of the subthalamic nucleus induces behavioral and movement disorders in monkeys</title></titleInfo><name type="personal"><namePart type="given">Carine</namePart><namePart type="family">Karachi</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><affiliation>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</affiliation><description>Correspondence: INSERM U679, Hôpital de la Salpêtrière, 47 Bd de l'Hôpital, 75651 Paris Cedex 13, France</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">David</namePart><namePart type="family">Grabli</namePart><namePart type="termsOfAddress">MD, PhD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><affiliation>Assistance Publique‐Hôpitaux de Paris, Groupe Pitié‐Salpêtrieère, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Nicolas</namePart><namePart type="family">Baup</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><affiliation>Department of Psychiatry, Centre Hospitalier Saint‐Anne, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Stéphanie</namePart><namePart type="family">Mounayar</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Dominique</namePart><namePart type="family">Tandé</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Chantal</namePart><namePart type="family">François</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Etienne C.</namePart><namePart type="family">Hirsch</namePart><namePart type="termsOfAddress">PhD</namePart><affiliation>INSERM, UMR_S679, Neurology and Experimental Therapeutics, Paris, France</affiliation><affiliation>UPMC Univ Paris 6, UMR_S679, Paris, France</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre authority="originalCategForm">article</genre><originInfo><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2009-06-15</dateIssued><dateCaptured encoding="w3cdtf">2008-10-21</dateCaptured><dateValid encoding="w3cdtf">2009-02-21</dateValid><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="figures">4</extent><extent unit="tables">2</extent><extent unit="references">27</extent><extent unit="words">6398</extent></physicalDescription><abstract lang="en">High‐frequency stimulation of the subthalamic nucleus (STN) in parkinsonian patients is reported to induce psychiatric effects. The likely explanation for these effects is the partitioning of the STN into sensorimotor, associative, and limbic anatomo‐functional territories. Thus, a specific neuronal dysfunction of the STN sensorimotor territory could lead to abnormal movements, whereas a dysfunction of the associative or limbic territory could lead to behavioral disturbances. To test this hypothesis, neuronal dysfunction of the STN was induced by microinjections of the GABA agonist muscimol, or antagonist bicucculline, in various parts of the nucleus in three monkeys. Stereotyped behaviors (licking and biting fingers) and/or violent hyperactivity were obtained with bicuculline injected into the anteromedial, associative, and limbic territories, whereas injections of muscimol induced no major effects. Abnormal limb movements (contralateral ballism) were obtained after muscimol or bicuculline injections into the posterolateral, sensorimotor territory. Control injections localized around the STN induced other effects (mainly torticollis), which underlines the specificity of STN injection effects. Our study supports the hypothesis that the anteromedial part of the STN is involved in behavioral control. © 2009 Movement Disorder Society</abstract><note type="content">*Potential conflict of interest: None reported.</note><note type="funding">The Tourette Syndrome Association (USA)</note><note type="funding">Institut National de la Santé et de la Recherche Médicale</note><note type="funding">Fondation pour la Recherche Médicale (FRM)</note><note type="funding">Association Française du Syndrome de Gilles de la Tourette (AFSGT)</note><note type="funding">Assistance Publique des Hôpitaux de Paris (APHP)</note><subject lang="en"><genre>Keywords</genre><topic>monkeys</topic><topic>subthalamic nucleus</topic><topic>microinjections</topic><topic>hemiballism</topic><topic>stereotypies</topic></subject><relatedItem type="host"><titleInfo><title>Movement Disorders</title></titleInfo><titleInfo type="abbreviated"><title>Mov. 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