Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.
Identifieur interne : 000640 ( PubMed/Checkpoint ); précédent : 000639; suivant : 000641Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.
Auteurs : Dayne A. Beccano-Kelly [Canada] ; Naila Kuhlmann [Canada] ; Igor Tatarnikov [Canada] ; Mattia Volta [Canada] ; Lise N. Munsie [Canada] ; Patrick Chou [Canada] ; Li-Ping Cao [Canada] ; Heather Han [Canada] ; Lucia Tapia [Canada] ; Matthew J. Farrer [Canada] ; Austen J. Milnerwood [Canada]Source :
- Frontiers in cellular neuroscience ; 2014.
Abstract
Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.
DOI: 10.3389/fncel.2014.00301
PubMed: 25309331
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Beccano-Kelly</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Kuhlmann, Naila" sort="Kuhlmann, Naila" uniqKey="Kuhlmann N" first="Naila" last="Kuhlmann">Naila Kuhlmann</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Graduate Program in Neuroscience, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Graduate Program in Neuroscience, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Tatarnikov, Igor" sort="Tatarnikov, Igor" uniqKey="Tatarnikov I" first="Igor" last="Tatarnikov">Igor Tatarnikov</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Volta, Mattia" sort="Volta, Mattia" uniqKey="Volta M" first="Mattia" last="Volta">Mattia Volta</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Munsie, Lise N" sort="Munsie, Lise N" uniqKey="Munsie L" first="Lise N" last="Munsie">Lise N. 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Beccano-Kelly</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Kuhlmann, Naila" sort="Kuhlmann, Naila" uniqKey="Kuhlmann N" first="Naila" last="Kuhlmann">Naila Kuhlmann</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Graduate Program in Neuroscience, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Graduate Program in Neuroscience, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Tatarnikov, Igor" sort="Tatarnikov, Igor" uniqKey="Tatarnikov I" first="Igor" last="Tatarnikov">Igor Tatarnikov</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Volta, Mattia" sort="Volta, Mattia" uniqKey="Volta M" first="Mattia" last="Volta">Mattia Volta</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Munsie, Lise N" sort="Munsie, Lise N" uniqKey="Munsie L" first="Lise N" last="Munsie">Lise N. Munsie</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Chou, Patrick" sort="Chou, Patrick" uniqKey="Chou P" first="Patrick" last="Chou">Patrick Chou</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Li Ping" sort="Cao, Li Ping" uniqKey="Cao L" first="Li-Ping" last="Cao">Li-Ping Cao</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Han, Heather" sort="Han, Heather" uniqKey="Han H" first="Heather" last="Han">Heather Han</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Tapia, Lucia" sort="Tapia, Lucia" uniqKey="Tapia L" first="Lucia" last="Tapia">Lucia Tapia</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Department of Medical Genetics, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Department of Medical Genetics, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Milnerwood, Austen J" sort="Milnerwood, Austen J" uniqKey="Milnerwood A" first="Austen J" last="Milnerwood">Austen J. Milnerwood</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Division of Neurology, University of British Columbia Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Division of Neurology, University of British Columbia Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><series><title level="j">Frontiers in cellular 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">Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">25309331</PMID><DateCreated><Year>2014</Year><Month>10</Month><Day>13</Day></DateCreated><DateCompleted><Year>2014</Year><Month>10</Month><Day>13</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><JournalIssue CitedMedium="Print"><Volume>8</Volume><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>Frontiers in cellular neuroscience</Title><ISOAbbreviation>Front Cell Neurosci</ISOAbbreviation></Journal><ArticleTitle>Synaptic function is modulated by LRRK2 and glutamate release is increased in cortical neurons of G2019S LRRK2 knock-in mice.</ArticleTitle><Pagination><MedlinePgn>301</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fncel.2014.00301</ELocationID><Abstract><AbstractText>Mutations in Leucine-Rich Repeat Kinase-2 (LRRK2) result in familial Parkinson's disease and the G2019S mutation alone accounts for up to 30% in some ethnicities. Despite this, the function of LRRK2 is largely undetermined although evidence suggests roles in phosphorylation, protein interactions, autophagy and endocytosis. Emerging reports link loss of LRRK2 to altered synaptic transmission, but the effects of the G2019S mutation upon synaptic release in mammalian neurons are unknown. To assess wild type and mutant LRRK2 in established neuronal networks, we conducted immunocytochemical, electrophysiological and biochemical characterization of >3 week old cortical cultures of LRRK2 knock-out, wild-type overexpressing and G2019S knock-in mice. Synaptic release and synapse numbers were grossly normal in LRRK2 knock-out cells, but discretely reduced glutamatergic activity and reduced synaptic protein levels were observed. Conversely, synapse density was modestly but significantly increased in wild-type LRRK2 overexpressing cultures although event frequency was not. In knock-in cultures, glutamate release was markedly elevated, in the absence of any change to synapse density, indicating that physiological levels of G2019S LRRK2 elevate probability of release. Several pre-synaptic regulatory proteins shown by others to interact with LRRK2 were expressed at normal levels in knock-in cultures; however, synapsin 1 phosphorylation was significantly reduced. Thus, perturbations to the pre-synaptic release machinery and elevated synaptic transmission are early neuronal effects of LRRK2 G2019S. Furthermore, the comparison of knock-in and overexpressing cultures suggests that one copy of the G2019S mutation has a more pronounced effect than an ~3-fold increase in LRRK2 protein. Mutant-induced increases in transmission may convey additional stressors to neuronal physiology that may eventually contribute to the pathogenesis of Parkinson's disease.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Beccano-Kelly</LastName><ForeName>Dayne A</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kuhlmann</LastName><ForeName>Naila</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Graduate Program in Neuroscience, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tatarnikov</LastName><ForeName>Igor</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Volta</LastName><ForeName>Mattia</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Munsie</LastName><ForeName>Lise N</ForeName><Initials>LN</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chou</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Li-Ping</ForeName><Initials>LP</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Han</LastName><ForeName>Heather</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Tapia</LastName><ForeName>Lucia</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farrer</LastName><ForeName>Matthew J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Department of Medical Genetics, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Milnerwood</LastName><ForeName>Austen J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Medical Genetics, University of British Columbia Vancouver, BC, Canada ; Djavad Mowafaghian Centre for Brain Health, Faculty of Medicine, University of British Columbia Vancouver, BC, Canada ; Division of Neurology, University of British Columbia Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>09</Month><Day>26</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Cell 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RefType="Cites"><RefSource>J Neurosci. 2014 Jan 22;34(4):1083-93</RefSource><PMID Version="1">24453301</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Brain Cell Biol. 2006 Jun;35(2-3):107-15</RefSource><PMID Version="1">17957477</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Neurosci. 2010 Sep 29;30(39):13138-49</RefSource><PMID Version="1">20881132</PMID></CommentsCorrections></CommentsCorrectionsList><OtherID Source="NLM">PMC4176085</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">G2019S</Keyword><Keyword MajorTopicYN="N">LRRK2</Keyword><Keyword MajorTopicYN="N">LRRK2 mutation</Keyword><Keyword MajorTopicYN="N">Parkinson disease</Keyword><Keyword MajorTopicYN="N">cortical culture</Keyword><Keyword MajorTopicYN="N">electrophysiology</Keyword><Keyword MajorTopicYN="N">transgenic mice</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>08</Month><Day>03</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>09</Month><Day>08</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2014</Year><Month>10</Month><Day>14</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25309331</ArticleId><ArticleId IdType="doi">10.3389/fncel.2014.00301</ArticleId><ArticleId IdType="pmc">PMC4176085</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Beccano Kelly, Dayne A" sort="Beccano Kelly, Dayne A" uniqKey="Beccano Kelly D" first="Dayne A" last="Beccano-Kelly">Dayne A. Beccano-Kelly</name></noRegion><name sortKey="Cao, Li Ping" sort="Cao, Li Ping" uniqKey="Cao L" first="Li-Ping" last="Cao">Li-Ping Cao</name><name sortKey="Chou, Patrick" sort="Chou, Patrick" uniqKey="Chou P" first="Patrick" last="Chou">Patrick Chou</name><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><name sortKey="Han, Heather" sort="Han, Heather" uniqKey="Han H" first="Heather" last="Han">Heather Han</name><name sortKey="Kuhlmann, Naila" sort="Kuhlmann, Naila" uniqKey="Kuhlmann N" first="Naila" last="Kuhlmann">Naila Kuhlmann</name><name sortKey="Milnerwood, Austen J" sort="Milnerwood, Austen J" uniqKey="Milnerwood A" first="Austen J" last="Milnerwood">Austen J. Milnerwood</name><name sortKey="Munsie, Lise N" sort="Munsie, Lise N" uniqKey="Munsie L" first="Lise N" last="Munsie">Lise N. Munsie</name><name sortKey="Tapia, Lucia" sort="Tapia, Lucia" uniqKey="Tapia L" first="Lucia" last="Tapia">Lucia Tapia</name><name sortKey="Tatarnikov, Igor" sort="Tatarnikov, Igor" uniqKey="Tatarnikov I" first="Igor" last="Tatarnikov">Igor Tatarnikov</name><name sortKey="Volta, Mattia" sort="Volta, Mattia" uniqKey="Volta M" first="Mattia" last="Volta">Mattia Volta</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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