Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.
Identifieur interne : 000558 ( PubMed/Corpus ); précédent : 000557; suivant : 000559Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.
Auteurs : Romain Carron ; Anton Filipchuk ; Romain Nardou ; Abhinav Singh ; Francois J. Michel ; Mark D. Humphries ; Constance HammondSource :
- Frontiers in systems neuroscience ; 2014.
Abstract
In Parkinson's disease (PD), cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1(-)/(-) mice, a genetic rodent model of the PARK6 variant of familial PD which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14-P21) wild-type or PINK1(-)/(-) mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN) is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1(-)/(-) M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1(-)/(-) M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS) of the STN. Our study describes an early excess of synchronization in the PINK1(-)/(-) cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.
DOI: 10.3389/fnsys.2014.00095
PubMed: 24904316
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Michel</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Humphries, Mark D" sort="Humphries, Mark D" uniqKey="Humphries M" first="Mark D" last="Humphries">Mark D. Humphries</name><affiliation><nlm:affiliation>Faculty of Life Sciences, University of Manchester Manchester, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hammond, Constance" sort="Hammond, Constance" uniqKey="Hammond C" first="Constance" last="Hammond">Constance Hammond</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24904316</idno><idno type="pmid">24904316</idno><idno type="doi">10.3389/fnsys.2014.00095</idno><idno type="wicri:Area/PubMed/Corpus">000558</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000558</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.</title><author><name sortKey="Carron, Romain" sort="Carron, Romain" uniqKey="Carron R" first="Romain" last="Carron">Romain Carron</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France ; APHM, Hopital de la Timone, Service de Neurochirurgie Fonctionnelle et Stereotaxique Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Filipchuk, Anton" sort="Filipchuk, Anton" uniqKey="Filipchuk A" first="Anton" last="Filipchuk">Anton Filipchuk</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France ; Instituto de Neurociencias, CSIC and Universidad Miguel Hernández, San Juan de Alicante Alicante, Spain.</nlm:affiliation></affiliation></author><author><name sortKey="Nardou, Romain" sort="Nardou, Romain" uniqKey="Nardou R" first="Romain" last="Nardou">Romain Nardou</name><affiliation><nlm:affiliation>B&A Therapeutics, at INMED Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Singh, Abhinav" sort="Singh, Abhinav" uniqKey="Singh A" first="Abhinav" last="Singh">Abhinav Singh</name><affiliation><nlm:affiliation>Faculty of Life Sciences, University of Manchester Manchester, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Michel, Francois J" sort="Michel, Francois J" uniqKey="Michel F" first="Francois J" last="Michel">Francois J. Michel</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Humphries, Mark D" sort="Humphries, Mark D" uniqKey="Humphries M" first="Mark D" last="Humphries">Mark D. Humphries</name><affiliation><nlm:affiliation>Faculty of Life Sciences, University of Manchester Manchester, UK.</nlm:affiliation></affiliation></author><author><name sortKey="Hammond, Constance" sort="Hammond, Constance" uniqKey="Hammond C" first="Constance" last="Hammond">Constance Hammond</name><affiliation><nlm:affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Frontiers in systems neuroscience</title><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">In Parkinson's disease (PD), cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1(-)/(-) mice, a genetic rodent model of the PARK6 variant of familial PD which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14-P21) wild-type or PINK1(-)/(-) mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN) is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1(-)/(-) M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1(-)/(-) M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS) of the STN. Our study describes an early excess of synchronization in the PINK1(-)/(-) cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">24904316</PMID><DateCreated><Year>2014</Year><Month>06</Month><Day>06</Day></DateCreated><DateCompleted><Year>2014</Year><Month>06</Month><Day>06</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>22</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><JournalIssue CitedMedium="Print"><Volume>8</Volume><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>Frontiers in systems neuroscience</Title><ISOAbbreviation>Front Syst Neurosci</ISOAbbreviation></Journal><ArticleTitle>Early hypersynchrony in juvenile PINK1(-)/(-) motor cortex is rescued by antidromic stimulation.</ArticleTitle><Pagination><MedlinePgn>95</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fnsys.2014.00095</ELocationID><Abstract><AbstractText>In Parkinson's disease (PD), cortical networks show enhanced synchronized activity but whether this precedes motor signs is unknown. We investigated this question in PINK1(-)/(-) mice, a genetic rodent model of the PARK6 variant of familial PD which shows impaired spontaneous locomotion at 16 months. We used two-photon calcium imaging and whole-cell patch clamp in slices from juvenile (P14-P21) wild-type or PINK1(-)/(-) mice. We designed a horizontal tilted cortico-subthalamic slice where the only connection between cortex and subthalamic nucleus (STN) is the hyperdirect cortico-subthalamic pathway. We report excessive correlation and synchronization in PINK1(-)/(-) M1 cortical networks 15 months before motor impairment. The percentage of correlated pairs of neurons and their strength of correlation were higher in the PINK1(-)/(-) M1 than in the wild type network and the synchronized network events involved a higher percentage of neurons. Both features were independent of thalamo-cortical pathways, insensitive to chronic levodopa treatment of pups, but totally reversed by antidromic invasion of M1 pyramidal neurons by axonal spikes evoked by high frequency stimulation (HFS) of the STN. Our study describes an early excess of synchronization in the PINK1(-)/(-) cortex and suggests a potential role of antidromic activation of cortical interneurons in network desynchronization. Such backward effect on interneurons activity may be of importance for HFS-induced network desynchronization.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Carron</LastName><ForeName>Romain</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France ; APHM, Hopital de la Timone, Service de Neurochirurgie Fonctionnelle et Stereotaxique Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Filipchuk</LastName><ForeName>Anton</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France ; Instituto de Neurociencias, CSIC and Universidad Miguel Hernández, San Juan de Alicante Alicante, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nardou</LastName><ForeName>Romain</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>B&A Therapeutics, at INMED Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Singh</LastName><ForeName>Abhinav</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Faculty of Life Sciences, University of Manchester Manchester, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Michel</LastName><ForeName>Francois J</ForeName><Initials>FJ</Initials><AffiliationInfo><Affiliation>Aix Marseille Université Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Humphries</LastName><ForeName>Mark D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Faculty of Life Sciences, University of Manchester Manchester, UK.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hammond</LastName><ForeName>Constance</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Aix Marseille Université Marseille, France ; Institut National de la Recherche Médicale et de la Santé, INMED, UMR 901 Marseille, France.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MR/J008648/1</GrantID><Agency>Medical Research Council</Agency><Country>United Kingdom</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>05</Month><Day>21</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Syst Neurosci</MedlineTA><NlmUniqueID>101477946</NlmUniqueID><ISSNLinking>1662-5137</ISSNLinking></MedlineJournalInfo><OtherID Source="NLM">PMC4033197</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">antidromic activation</Keyword><Keyword MajorTopicYN="N">cortical network</Keyword><Keyword MajorTopicYN="N">deep brain stimulation (DBS)</Keyword><Keyword MajorTopicYN="N">familial Parkinson</Keyword><Keyword MajorTopicYN="N">synchronization</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>03</Month><Day>02</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>05</Month><Day>05</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>6</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>6</Month><Day>7</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>6</Month><Day>7</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">24904316</ArticleId><ArticleId IdType="doi">10.3389/fnsys.2014.00095</ArticleId><ArticleId IdType="pmc">PMC4033197</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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