Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice
Identifieur interne : 002203 ( Ncbi/Merge ); précédent : 002202; suivant : 002204Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice
Auteurs : D. Gagnon [Canada] ; S. Petryszyn [Canada] ; M. G. Sanchez [Canada] ; C. Bories [Canada] ; J. M. Beaulieu [Canada] ; Y. De Koninck [Canada] ; A. Parent [Canada] ; M. Parent [Canada]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
Abstract
The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (
Url:
DOI: 10.1038/srep41432
PubMed: 28128287
PubMed Central: 5269744
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Petryszyn</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sanchez, M G" sort="Sanchez, M G" uniqKey="Sanchez M" first="M. G." last="Sanchez">M. G. Sanchez</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bories, C" sort="Bories, C" uniqKey="Bories C" first="C." last="Bories">C. Bories</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Beaulieu, J M" sort="Beaulieu, J M" uniqKey="Beaulieu J" first="J. M." last="Beaulieu">J. M. Beaulieu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Koninck, Y" sort="De Koninck, Y" uniqKey="De Koninck Y" first="Y." last="De Koninck">Y. De Koninck</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Parent, A" sort="Parent, A" uniqKey="Parent A" first="A." last="Parent">A. 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Parent</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">28128287</idno><idno type="pmc">5269744</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269744</idno><idno type="RBID">PMC:5269744</idno><idno type="doi">10.1038/srep41432</idno><date when="2017">2017</date><idno type="wicri:Area/Pmc/Corpus">000204</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000204</idno><idno type="wicri:Area/Pmc/Curation">000204</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000204</idno><idno type="wicri:Area/Pmc/Checkpoint">000004</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000004</idno><idno type="wicri:Area/Ncbi/Merge">002203</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Striatal Neurons Expressing D<sub>1</sub> and D<sub>2</sub> Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice</title><author><name sortKey="Gagnon, D" sort="Gagnon, D" uniqKey="Gagnon D" first="D." last="Gagnon">D. Gagnon</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Petryszyn, S" sort="Petryszyn, S" uniqKey="Petryszyn S" first="S." last="Petryszyn">S. Petryszyn</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Sanchez, M G" sort="Sanchez, M G" uniqKey="Sanchez M" first="M. G." last="Sanchez">M. G. Sanchez</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bories, C" sort="Bories, C" uniqKey="Bories C" first="C." last="Bories">C. Bories</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Beaulieu, J M" sort="Beaulieu, J M" uniqKey="Beaulieu J" first="J. M." last="Beaulieu">J. M. Beaulieu</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="De Koninck, Y" sort="De Koninck, Y" uniqKey="De Koninck Y" first="Y." last="De Koninck">Y. De Koninck</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Parent, A" sort="Parent, A" uniqKey="Parent A" first="A." last="Parent">A. Parent</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Parent, M" sort="Parent, M" uniqKey="Parent M" first="M." last="Parent">M. Parent</name><affiliation wicri:level="1"><nlm:aff id="a1"><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D<sub>1</sub> or D<sub>2</sub> dopamine receptor. Consequences on MSNs expressing both receptors (D<sub>1</sub>/D<sub>2</sub> MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D<sub>1</sub>/D<sub>2</sub> MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (<italic>Drd1a</italic>-tdTomato/<italic>Drd2</italic>-EGFP) to sham-lesioned animals. D<sub>1</sub>/D<sub>2</sub> MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D<sub>1</sub> and D<sub>2</sub> MSNs, D<sub>1</sub>/D<sub>2</sub> MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D<sub>1</sub>/D<sub>2</sub> MSNs, but also of D<sub>1</sub> and D<sub>2</sub> MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D<sub>1</sub> and D<sub>2</sub> MSNs, the extent of dendritic arborization of D<sub>1</sub>/D<sub>2</sub> MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D<sub>1</sub>/D<sub>2</sub> MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Graveland, G A" uniqKey="Graveland G">G. A. Graveland</name></author><author><name sortKey="Difiglia, M" uniqKey="Difiglia M">M. DiFiglia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gerfen, C R" uniqKey="Gerfen C">C. R. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">28128287</article-id><article-id pub-id-type="pmc">5269744</article-id><article-id pub-id-type="pii">srep41432</article-id><article-id pub-id-type="doi">10.1038/srep41432</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Striatal Neurons Expressing D<sub>1</sub> and D<sub>2</sub> Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Gagnon</surname><given-names>D.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Petryszyn</surname><given-names>S.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sanchez</surname><given-names>M. G.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bories</surname><given-names>C.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Beaulieu</surname><given-names>J. M.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>De Koninck</surname><given-names>Y.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Parent</surname><given-names>A.</given-names></name><xref ref-type="aff" rid="a1">1</xref></contrib><contrib contrib-type="author"><name><surname>Parent</surname><given-names>M.</given-names></name><xref ref-type="corresp" rid="c1">a</xref><xref ref-type="aff" rid="a1">1</xref></contrib><aff id="a1"><label>1</label><institution>Centre de recherche de l’Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Faculty of medicine, Université Laval</institution>, Quebec City, QC,<country>Canada</country></aff></contrib-group><author-notes><corresp id="c1"><label>a</label><email>martin.parent@fmed.ulaval.ca</email></corresp></author-notes><pub-date pub-type="epub"><day>27</day><month>01</month><year>2017</year></pub-date><pub-date pub-type="collection"><year>2017</year></pub-date><volume>7</volume><elocation-id>41432</elocation-id><history><date date-type="received"><day>20</day><month>09</month><year>2016</year></date><date date-type="accepted"><day>19</day><month>12</month><year>2016</year></date></history><permissions><copyright-statement>Copyright © 2017, The Author(s)</copyright-statement><copyright-year>2017</copyright-year><copyright-holder>The Author(s)</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><pmc-comment>author-paid</pmc-comment>
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link></license-p></license></permissions><abstract><p>The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D<sub>1</sub> or D<sub>2</sub> dopamine receptor. Consequences on MSNs expressing both receptors (D<sub>1</sub>/D<sub>2</sub> MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D<sub>1</sub>/D<sub>2</sub> MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (<italic>Drd1a</italic>-tdTomato/<italic>Drd2</italic>-EGFP) to sham-lesioned animals. D<sub>1</sub>/D<sub>2</sub> MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D<sub>1</sub> and D<sub>2</sub> MSNs, D<sub>1</sub>/D<sub>2</sub> MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D<sub>1</sub>/D<sub>2</sub> MSNs, but also of D<sub>1</sub> and D<sub>2</sub> MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D<sub>1</sub> and D<sub>2</sub> MSNs, the extent of dendritic arborization of D<sub>1</sub>/D<sub>2</sub> MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D<sub>1</sub>/D<sub>2</sub> MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease.</p></abstract></article-meta></front><floats-group><fig id="f1"><label>Figure 1</label><caption><title>Assessment of the dopaminergic lesion induced by 6-OHDA injection in the medial forebrain bundle.</title><p>(<bold>a)</bold> Transverse section taken through the substantia nigra <italic>pars compacta</italic> (SNc) and the ventral tegmental area (VTA) that was immunostained for tyrosine hydroxylase (TH) to assess the dopaminergic lesion induced by stereotaxic injection of 6-OHDA in the right medial forebrain bundle. (<bold>b</bold>) Histogram showing the percentage of TH + cell loss in the SNc and the VTA, as expressed in percentage of intact side. (<bold>c</bold>) Transverse section taken through the striatum (STR) and immunostained for TH. (<bold>d</bold>) Histogram showing immunoreactivity of the STR and the nucleus accumbens (Acb) for the tyrosine hydroxylase (TH) and the dopamine transporter (DAT) in the 6-OHDA-lesioned side, as expressed in percentage of intact side. (<bold>e</bold>) Behavioural response induced by 6-OHDA lesion, as shown in number of contralateral and ipsilateral spontaneous rotations observed in 10 minutes. *<italic>P</italic> < 0.05, **P < 0.01, ***P < 0.001 for intact side vs. 6-OHDA-lesioned side, ****P < 0.0001 for ipsilateral vs. contralateral rotations, by Mann-Whitney test.</p></caption><graphic xlink:href="srep41432-f1"></graphic></fig><fig id="f2"><label>Figure 2</label><caption><title>Neurochemical content of the D<sub>1</sub>/D<sub>2</sub> MSNs.</title><p>Transverse sections taken from the dorsolateral striatum of a D<sub>1</sub>/D<sub>2</sub> transgenic mouse that were immunostained for enkephalin (ENK, <bold>a–d</bold>) or dynorphin (DYN, <bold>e–h</bold>). Thin arrows indicate D<sub>1</sub> MSNs, thick arrows point to D<sub>2</sub> MSNs and arrowheads to D<sub>1</sub>/D<sub>2</sub> MSNs. The D<sub>1</sub>/D<sub>2</sub> MSNs are immunoreactive for dynorphin but not for enkephalin in the D<sub>1</sub>/D<sub>2</sub> transgenic mouse.</p></caption><graphic xlink:href="srep41432-f2"></graphic></fig><fig id="f3"><label>Figure 3</label><caption><title>Densities of D<sub>1</sub>, D<sub>2</sub> and D<sub>1</sub>/D<sub>2</sub> MSNs in sham and 6-OHDA-lesioned mice.</title><p>Histograms showing the density of D<sub>1</sub> (<bold>a</bold>), D<sub>2</sub> (<bold>b</bold>) and D<sub>1</sub>/D<sub>2</sub> (<bold>c</bold>) MSNs in different regions of the striatum (STR) and the nucleus accumbens (Acb) of sham and 6-OHDA-lesioned mice. <sup>#</sup><italic>P</italic> < 0.05, <sup>##</sup><italic>P</italic> < 0.01 vs. the shell compartment of the Acb and <sup>@</sup><italic>P</italic> < 0.05, <sup>@@</sup><italic>P</italic> < 0.01 vs. the core compartment of the Acb, by Kruskal-Wallis test.</p></caption><graphic xlink:href="srep41432-f3"></graphic></fig><fig id="f4"><label>Figure 4</label><caption><title>Regional distribution of D<sub>1</sub>/D<sub>2</sub> MSNs in the dorsal striatum and the nucleus accumbens.</title><p><bold>(a</bold>,<bold>b)</bold> Schematic representations of transverse sections taken at 0.26, −0.94 and 1.10 mm from bregma on which sectors that were sampled to provide unbiased stereological estimation of the number of D<sub>1</sub>, D<sub>2</sub> and D<sub>1</sub>/D<sub>2</sub> MSNs in the striatum (STR, <bold>a</bold>) and the nucleus accumbens (Acb, (<bold>b</bold>) are delineated. (<bold>c,d)</bold> Schematic representations of the distribution of D<sub>1</sub>/D<sub>2</sub> MSNs at the pre and post-commissural level of the STR (<bold>c</bold>) as well as in the core (AcbC) and the shell (AcbSh) of the nucleus accumbens. The transverse section shown in (<bold>b</bold>) was immunostained for calbindin and used to delineate the AcbC from the AcbSh.</p></caption><graphic xlink:href="srep41432-f4"></graphic></fig><fig id="f5"><label>Figure 5</label><caption><title>Dendritic domains of the D<sub>1</sub>, D<sub>2</sub> and D<sub>1</sub>/D<sub>2</sub> MSNs in sham-lesioned mice</title><p>. <bold>(a–c)</bold> Histograms showing the total dendritic length (<bold>a</bold>), the number of dendritic branch points (<bold>b</bold>) and the overall spine density (<bold>c</bold>) of the D<sub>1</sub> (red), the D<sub>2</sub> (green) and the D<sub>1</sub>/D<sub>2</sub> (yellow) striatal MSNs in sham-lesioned mice. (<bold>d)</bold> Sholl analysis of spine density of the 3 types of MSNs, as measured in sham-lesioned mice. *<italic>P</italic> < 0.05, **<italic>P</italic> < 0.01, ***<italic>P</italic> < 0.001, ****<italic>P</italic> < 0.0001 for D<sub>1</sub> vs. D<sub>2</sub> vs. D<sub>1</sub>/D<sub>2</sub> by One-way (<bold>a–c</bold>) or Two-way (<bold>d</bold>) ANOVA, followed by Bonferroni’s multiple comparison test.</p></caption><graphic xlink:href="srep41432-f5"></graphic></fig><fig id="f6"><label>Figure 6</label><caption><title>Dendritic arborization of the D<sub>1</sub>, D<sub>2</sub> and D<sub>1</sub>/D<sub>2</sub> MSNs in 6-OHDA-lesioned mice.</title><p>Histograms showing the total dendritic length and the number of dendritic branch points in sham (plain columns) and 6-OHDA (hatched columns) lesioned mice. The center and right columns provide schematic representations of D<sub>1</sub> (red), D<sub>2</sub> (green) and D<sub>1</sub>/D<sub>2</sub> (yellow) MSNs dendritic arborization in sham (center column) and 6-OHDA (right column) lesioned mice. *<italic>P</italic> < 0.05, ****<italic>P</italic> < 0.0001 for sham vs. 6-OHDA-lesioned mice, by Student’s T-test.</p></caption><graphic xlink:href="srep41432-f6"></graphic></fig><fig id="f7"><label>Figure 7</label><caption><title>Dendritic spine density of the D<sub>1</sub>, D<sub>2</sub> and D<sub>1</sub>/D<sub>2</sub> MSNs in sham and 6-OHDA-lesioned mice.</title><p>Sholl analysis of spine density (left column) and histograms showing the overall spine density (center column) of the D<sub>1</sub> ((<bold>a</bold>), red), D<sub>2</sub> ((<bold>b</bold>), green) and D<sub>1</sub>/D<sub>2</sub> ((<bold>c</bold>), yellow) striatal MSNs in sham (circles and plain columns) and 6-OHDA (square and hatched columns) lesioned mice. The right column provides representative examples of dendritic segments belonging to the D<sub>1</sub>, D<sub>2</sub> or D<sub>1</sub>/D<sub>2</sub> MSNs that were filled with Lucifer yellow in sham and 6-OHDA-lesioned mice. *<italic>P</italic> < 0.05, **<italic>P</italic> < 0.01, ***<italic>P</italic> < 0.001, ****<italic>P</italic> < 0.0001 for sham vs. 6-OHDA by a Student’s T-test (histograms) or Two-way ANOVA followed by Bonferroni’s multiple comparison test (Sholl analysis).</p></caption><graphic xlink:href="srep41432-f7"></graphic></fig><fig id="f8"><label>Figure 8</label><caption><title>D<sub>1</sub>/D<sub>2</sub> double BAC transgenic mice.</title><p>Confocal images from the Drd1a-tdTomato/Drd2-EGFP double BAC transgenic mice (D<sub>1</sub>/D<sub>2</sub>) in which the expression of a red fluorescent protein (tdTomato) is under control of the D<sub>1</sub> promoter and the expression of a green fluorescent protein (EGFP) is under control of the D<sub>2</sub> promoter. (<bold>a</bold>) Confocal image of a sagittal section from a D<sub>1</sub>/D<sub>2</sub> transgenic mouse taken through the striatum (STR) and the substantia nigra (SN). (<bold>b)</bold> Example of a Lucifer yellow-injected MSN located in the dorsal STR. (<bold>c–e)</bold> High magnification of striatal MSNs that contain the D<sub>1</sub> (red, thin arrows), the D<sub>2</sub> (green, thick arrows) or both D<sub>1</sub>/D<sub>2</sub> (yellow, arrowheads) dopamine receptors.</p></caption><graphic xlink:href="srep41432-f8"></graphic></fig></floats-group></pmc><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Gagnon, D" sort="Gagnon, D" uniqKey="Gagnon D" first="D." last="Gagnon">D. Gagnon</name></noRegion><name sortKey="Beaulieu, J M" sort="Beaulieu, J M" uniqKey="Beaulieu J" first="J. M." last="Beaulieu">J. M. Beaulieu</name><name sortKey="Bories, C" sort="Bories, C" uniqKey="Bories C" first="C." last="Bories">C. Bories</name><name sortKey="De Koninck, Y" sort="De Koninck, Y" uniqKey="De Koninck Y" first="Y." last="De Koninck">Y. De Koninck</name><name sortKey="Parent, A" sort="Parent, A" uniqKey="Parent A" first="A." last="Parent">A. Parent</name><name sortKey="Parent, M" sort="Parent, M" uniqKey="Parent M" first="M." last="Parent">M. Parent</name><name sortKey="Petryszyn, S" sort="Petryszyn, S" uniqKey="Petryszyn S" first="S." last="Petryszyn">S. Petryszyn</name><name sortKey="Sanchez, M G" sort="Sanchez, M G" uniqKey="Sanchez M" first="M. G." last="Sanchez">M. G. Sanchez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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