Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.
Identifieur interne : 000653 ( PubMed/Checkpoint ); précédent : 000652; suivant : 000654Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.
Auteurs : Sherri L. Thiele [Canada] ; Betty Chen [Canada] ; Charlotte Lo [Canada] ; Tracey S. Gertler [États-Unis] ; Ruth Warre [Canada] ; James D. Surmeier [États-Unis] ; Jonathan M. Brotchie [Canada] ; Joanne E. Nash [Canada]Source :
- Neurobiology of disease [ 1095-953X ] ; 2014.
English descriptors
- KwdEn :
- Animals, Animals, Newborn, Antiparkinson Agents (adverse effects), Corpus Striatum (pathology), Disease Models, Animal, Dopamine Agents (pharmacology), Dyskinesia, Drug-Induced (etiology), Dyskinesia, Drug-Induced (pathology), Excitatory Postsynaptic Potentials (drug effects), Functional Laterality, Green Fluorescent Proteins (genetics), Green Fluorescent Proteins (metabolism), In Vitro Techniques, Levodopa (adverse effects), Mice, Mice, Transgenic, Neural Pathways (pathology), Neuronal Plasticity (drug effects), Neuronal Plasticity (physiology), Oxidopamine (toxicity), Parkinsonian Disorders (chemically induced), Parkinsonian Disorders (drug therapy), Purinergic Agents (pharmacology), Receptor, Adenosine A2A (genetics), Receptor, Adenosine A2A (metabolism), Receptors, Dopamine D1 (genetics), Receptors, Dopamine D1 (metabolism).
- MESH :
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemically induced : Parkinsonian Disorders.
- drug effects : Excitatory Postsynaptic Potentials, Neuronal Plasticity.
- drug therapy : Parkinsonian Disorders.
- etiology : Dyskinesia, Drug-Induced.
- chemical , genetics : Green Fluorescent Proteins, Receptor, Adenosine A2A, Receptors, Dopamine D1.
- chemical , metabolism : Green Fluorescent Proteins, Receptor, Adenosine A2A, Receptors, Dopamine D1.
- pathology : Corpus Striatum, Dyskinesia, Drug-Induced, Neural Pathways.
- chemical , pharmacology : Dopamine Agents, Purinergic Agents.
- physiology : Neuronal Plasticity.
- chemical , toxicity : Oxidopamine.
- Animals, Animals, Newborn, Disease Models, Animal, Functional Laterality, In Vitro Techniques, Mice, Mice, Transgenic.
Abstract
Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs, which underlies the symptomatic benefits of l-DOPA. Switching from bidirectional to unidirectional plasticity drives global changes in striatal pathway excitability, and underpins parkinsonism and dyskinesia.
DOI: 10.1016/j.nbd.2014.08.006
PubMed: 25171793
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Thiele</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4</wicri:regionArea><wicri:noRegion>ON M1C 1A4</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Betty" sort="Chen, Betty" uniqKey="Chen B" first="Betty" last="Chen">Betty Chen</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4</wicri:regionArea><wicri:noRegion>ON M1C 1A4</wicri:noRegion></affiliation></author><author><name sortKey="Lo, Charlotte" sort="Lo, Charlotte" uniqKey="Lo C" first="Charlotte" last="Lo">Charlotte Lo</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4</wicri:regionArea><wicri:noRegion>ON M1C 1A4</wicri:noRegion></affiliation></author><author><name sortKey="Gertler, Tracey S" sort="Gertler, Tracey S" uniqKey="Gertler T" first="Tracey S" last="Gertler">Tracey S. Gertler</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Warre, Ruth" sort="Warre, Ruth" uniqKey="Warre R" first="Ruth" last="Warre">Ruth Warre</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4</wicri:regionArea><wicri:noRegion>ON M1C 1A4</wicri:noRegion></affiliation></author><author><name sortKey="Surmeier, James D" sort="Surmeier, James D" uniqKey="Surmeier J" first="James D" last="Surmeier">James D. Surmeier</name><affiliation wicri:level="2"><nlm:affiliation>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name><affiliation wicri:level="1"><nlm:affiliation>Division of Brain Imaging & Behaviour Systems - Neuroscience, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Brain Imaging & Behaviour Systems - Neuroscience, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON M5T 2S8</wicri:regionArea><wicri:noRegion>ON M5T 2S8</wicri:noRegion></affiliation></author><author><name sortKey="Nash, Joanne E" sort="Nash, Joanne E" uniqKey="Nash J" first="Joanne E" last="Nash">Joanne E. Nash</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. Electronic address: jnash@utsc.utoronto.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4</wicri:regionArea><wicri:noRegion>ON M1C 1A4</wicri:noRegion></affiliation></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Animals, Newborn</term><term>Antiparkinson Agents (adverse effects)</term><term>Corpus Striatum (pathology)</term><term>Disease Models, Animal</term><term>Dopamine Agents (pharmacology)</term><term>Dyskinesia, Drug-Induced (etiology)</term><term>Dyskinesia, Drug-Induced (pathology)</term><term>Excitatory Postsynaptic Potentials (drug effects)</term><term>Functional Laterality</term><term>Green Fluorescent Proteins (genetics)</term><term>Green Fluorescent Proteins (metabolism)</term><term>In Vitro Techniques</term><term>Levodopa (adverse effects)</term><term>Mice</term><term>Mice, Transgenic</term><term>Neural Pathways (pathology)</term><term>Neuronal Plasticity (drug effects)</term><term>Neuronal Plasticity (physiology)</term><term>Oxidopamine (toxicity)</term><term>Parkinsonian Disorders (chemically induced)</term><term>Parkinsonian Disorders (drug therapy)</term><term>Purinergic Agents (pharmacology)</term><term>Receptor, Adenosine A2A (genetics)</term><term>Receptor, Adenosine A2A (metabolism)</term><term>Receptors, Dopamine D1 (genetics)</term><term>Receptors, Dopamine D1 (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Excitatory Postsynaptic Potentials</term><term>Neuronal Plasticity</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Dyskinesia, Drug-Induced</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Green Fluorescent Proteins</term><term>Receptor, Adenosine A2A</term><term>Receptors, Dopamine D1</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Green Fluorescent Proteins</term><term>Receptor, Adenosine A2A</term><term>Receptors, Dopamine D1</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term><term>Dyskinesia, Drug-Induced</term><term>Neural Pathways</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Dopamine Agents</term><term>Purinergic Agents</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Neuronal Plasticity</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Animals, Newborn</term><term>Disease Models, Animal</term><term>Functional Laterality</term><term>In Vitro Techniques</term><term>Mice</term><term>Mice, Transgenic</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs, which underlies the symptomatic benefits of l-DOPA. Switching from bidirectional to unidirectional plasticity drives global changes in striatal pathway excitability, and underpins parkinsonism and dyskinesia.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25171793</PMID><DateCreated><Year>2014</Year><Month>09</Month><Day>29</Day></DateCreated><DateCompleted><Year>2015</Year><Month>06</Month><Day>02</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-953X</ISSN><JournalIssue CitedMedium="Internet"><Volume>71</Volume><PubDate><Year>2014</Year><Month>Nov</Month></PubDate></JournalIssue><Title>Neurobiology of disease</Title><ISOAbbreviation>Neurobiol. Dis.</ISOAbbreviation></Journal><ArticleTitle>Selective loss of bi-directional synaptic plasticity in the direct and indirect striatal output pathways accompanies generation of parkinsonism and l-DOPA induced dyskinesia in mouse models.</ArticleTitle><Pagination><MedlinePgn>334-44</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.nbd.2014.08.006</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0969-9961(14)00235-6</ELocationID><Abstract><AbstractText>Parkinsonian symptoms arise due to over-activity of the indirect striatal output pathway, and under-activity of the direct striatal output pathway. l-DOPA-induced dyskinesia (LID) is caused when the opposite circuitry problems are established, with the indirect pathway becoming underactive, and the direct pathway becoming over-active. Here, we define synaptic plasticity abnormalities in these pathways associated with parkinsonism, symptomatic benefits of l-DOPA, and LID. We applied spike-timing dependent plasticity protocols to cortico-striatal synapses in slices from 6-OHDA-lesioned mouse models of parkinsonism and LID, generated in BAC transgenic mice with eGFP targeting the direct or indirect output pathways, with and without l-DOPA present. In naïve mice, bidirectional synaptic plasticity, i.e. LTP and LTD, was induced, resulting in an EPSP amplitude change of approximately 50% in each direction in both striatal output pathways, as shown previously. In parkinsonism and dyskinesia, both pathways exhibited unidirectional plasticity, irrespective of stimulation paradigm. In parkinsonian animals, the indirect pathway only exhibited LTP (LTP protocol: 143.5±14.6%; LTD protocol 177.7±22.3% of baseline), whereas the direct pathway only showed LTD (LTP protocol: 74.3±4.0% and LTD protocol: 63.3±8.7%). A symptomatic dose of l-DOPA restored bidirectional plasticity on both pathways to levels comparable to naïve animals (Indirect pathway: LTP protocol: 124.4±22.0% and LTD protocol: 52.1±18.5% of baseline. Direct pathway: LTP protocol: 140.7±7.3% and LTD protocol: 58.4±6.0% of baseline). In dyskinesia, in the presence of l-DOPA, the indirect pathway exhibited only LTD (LTP protocol: 68.9±21.3% and LTD protocol 52.0±14.2% of baseline), whereas in the direct pathway, only LTP could be induced (LTP protocol: 156.6±13.2% and LTD protocol 166.7±15.8% of baseline). We conclude that normal motor control requires bidirectional plasticity of both striatal outputs, which underlies the symptomatic benefits of l-DOPA. Switching from bidirectional to unidirectional plasticity drives global changes in striatal pathway excitability, and underpins parkinsonism and dyskinesia.</AbstractText><CopyrightInformation>Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Thiele</LastName><ForeName>Sherri L</ForeName><Initials>SL</Initials><AffiliationInfo><Affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Betty</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lo</LastName><ForeName>Charlotte</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gertler</LastName><ForeName>Tracey S</ForeName><Initials>TS</Initials><AffiliationInfo><Affiliation>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Warre</LastName><ForeName>Ruth</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Surmeier</LastName><ForeName>James D</ForeName><Initials>JD</Initials><AffiliationInfo><Affiliation>Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Brotchie</LastName><ForeName>Jonathan M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Division of Brain Imaging & Behaviour Systems - Neuroscience, Toronto Western Research Institute, 399 Bathurst Street, Toronto, ON M5T 2S8, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nash</LastName><ForeName>Joanne E</ForeName><Initials>JE</Initials><AffiliationInfo><Affiliation>Centre for Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON M1C 1A4, Canada. Electronic address: jnash@utsc.utoronto.ca.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 DA012958</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>R01 NS034696</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>08</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurobiol Dis</MedlineTA><NlmUniqueID>9500169</NlmUniqueID><ISSNLinking>0969-9961</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000978">Antiparkinson 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PubStatus="pubmed"><Year>2014</Year><Month>8</Month><Day>31</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>6</Month><Day>3</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25171793</ArticleId><ArticleId IdType="pii">S0969-9961(14)00235-6</ArticleId><ArticleId IdType="doi">10.1016/j.nbd.2014.08.006</ArticleId><ArticleId IdType="pmc">PMC4486078</ArticleId><ArticleId IdType="mid">NIHMS687314</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Illinois</li></region></list><tree><country name="Canada"><noRegion><name sortKey="Thiele, Sherri L" sort="Thiele, Sherri L" uniqKey="Thiele S" first="Sherri L" last="Thiele">Sherri L. Thiele</name></noRegion><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name><name sortKey="Chen, Betty" sort="Chen, Betty" uniqKey="Chen B" first="Betty" last="Chen">Betty Chen</name><name sortKey="Lo, Charlotte" sort="Lo, Charlotte" uniqKey="Lo C" first="Charlotte" last="Lo">Charlotte Lo</name><name sortKey="Nash, Joanne E" sort="Nash, Joanne E" uniqKey="Nash J" first="Joanne E" last="Nash">Joanne E. Nash</name><name sortKey="Warre, Ruth" sort="Warre, Ruth" uniqKey="Warre R" first="Ruth" last="Warre">Ruth Warre</name></country><country name="États-Unis"><region name="Illinois"><name sortKey="Gertler, Tracey S" sort="Gertler, Tracey S" uniqKey="Gertler T" first="Tracey S" last="Gertler">Tracey S. Gertler</name></region><name sortKey="Surmeier, James D" sort="Surmeier, James D" uniqKey="Surmeier J" first="James D" last="Surmeier">James D. 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