Elimination of the Vesicular Acetylcholine Transporter in the Striatum Reveals Regulation of Behaviour by Cholinergic-Glutamatergic Co-Transmission
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{"title"=>"Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission", "type"=>"journal", "authors"=>[{"first_name"=>"Monica S.", "last_name"=>"Guzman", "scopus_author_id"=>"37096974100"}, {"first_name"=>"Xavier", "last_name"=>"de Jaeger", "scopus_author_id"=>"16042135200"}, {"first_name"=>"Sanda", "last_name"=>"Raulic", "scopus_author_id"=>"8761925500"}, {"first_name"=>"Ivana A.", "last_name"=>"Souza", "scopus_author_id"=>"35855309700"}, {"first_name"=>"Alex X.", "last_name"=>"Li", "scopus_author_id"=>"35334608000"}, {"first_name"=>"Susanne", "last_name"=>"Schmid", "scopus_author_id"=>"35509479800"}, {"first_name"=>"Ravi S.", "last_name"=>"Menon", "scopus_author_id"=>"14056524100"}, {"first_name"=>"Raul R.", "last_name"=>"Gainetdinov", "scopus_author_id"=>"7006340278"}, {"first_name"=>"Marc G.", "last_name"=>"Caron", "scopus_author_id"=>"35371418700"}, {"first_name"=>"Robert", "last_name"=>"Bartha", "scopus_author_id"=>"7006517153"}, {"first_name"=>"Vania F.", "last_name"=>"Prado", "scopus_author_id"=>"7006609498"}, {"first_name"=>"Marco A.M.", "last_name"=>"Prado", "scopus_author_id"=>"35595960300"}], "year"=>2011, "source"=>"PLoS Biology", "identifiers"=>{"issn"=>"15449173", "scopus"=>"2-s2.0-82455192840", "sgr"=>"82455192840", "pui"=>"363017196", "isbn"=>"1545-7885 (Electronic)\\r1544-9173 (Linking)", "pmid"=>"22087075", "doi"=>"10.1371/journal.pbio.1001194"}, "id"=>"acd38313-930d-3066-982d-e9d953befc3f", "abstract"=>"Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.", "link"=>"http://www.mendeley.com/research/elimination-vesicular-acetylcholine-transporter-striatum-reveals-regulation-behaviour-cholinergicglu", "reader_count"=>97, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>8, "Student > Doctoral Student"=>5, "Researcher"=>31, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>6, "Student > Master"=>7, "Other"=>5, "Student > Bachelor"=>3, "Professor"=>7}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>8, "Student > Doctoral Student"=>5, "Researcher"=>31, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>6, "Student > Master"=>7, "Other"=>5, "Student > Bachelor"=>3, "Professor"=>7}, "reader_count_by_subject_area"=>{"Unspecified"=>6, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>9, "Agricultural and Biological Sciences"=>53, "Neuroscience"=>19, "Psychology"=>3, "Chemistry"=>1, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>9}, "Neuroscience"=>{"Neuroscience"=>19}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>2}, "Psychology"=>{"Psychology"=>3}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>53}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>6}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Argentina"=>1, "United States"=>5, "Brazil"=>2, "United Kingdom"=>1, "France"=>3, "Chile"=>1, "Australia"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/362936", "https://ndownloader.figshare.com/files/362991", "https://ndownloader.figshare.com/files/363018", "https://ndownloader.figshare.com/files/363042", "https://ndownloader.figshare.com/files/363063", "https://ndownloader.figshare.com/files/363107", "https://ndownloader.figshare.com/files/363146"], "description"=>"<div><p>Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. These neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. Consequently cholinergic neurons can release both neurotransmitters, making it difficult to discern their individual contributions for the regulation of striatal functions. Here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (VAChT) from striatal cholinergic neurons. Analysis of several behavioural parameters indicates that elimination of VAChT had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion, cocaine-induced hyperactivity, or its reward properties. However, dopaminergic sensitivity of medium spiny neurons (MSN) and the behavioural outputs in response to direct dopaminergic agonists were enhanced, likely due to increased expression/function of dopamine receptors in the striatum. These observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. Our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. The data also raise the possibility of using VAChT as a target to boost dopaminergic function and decrease high striatal cholinergic activity, common neurochemical alterations in individuals affected with Parkinson's disease.</p> </div>", "links"=>[], "tags"=>["elimination", "vesicular", "acetylcholine", "transporter", "striatum", "reveals", "behaviour", "cholinergic-glutamatergic", "co-transmission"], "article_id"=>131716, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.s001", "https://dx.doi.org/10.1371/journal.pbio.1001194.s002", "https://dx.doi.org/10.1371/journal.pbio.1001194.s003", "https://dx.doi.org/10.1371/journal.pbio.1001194.s004", "https://dx.doi.org/10.1371/journal.pbio.1001194.s005", "https://dx.doi.org/10.1371/journal.pbio.1001194.s006", "https://dx.doi.org/10.1371/journal.pbio.1001194.s007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Elimination_of_the_Vesicular_Acetylcholine_Transporter_in_the_Striatum_Reveals_Regulation_of_Behaviour_by_Cholinergic_Glutamatergic_Co_Transmission/131716", "title"=>"Elimination of the Vesicular Acetylcholine Transporter in the Striatum Reveals Regulation of Behaviour by Cholinergic-Glutamatergic Co-Transmission", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-11-08 00:28:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/714760"], "description"=>"<p>(a) Expression pattern of Cre detected by staining for YFP in the brain of D2-Cre;Rosa26-YFP mice. (b) Sections from different regions of the central nervous system were immunostained for CHT1 (Red) and YFP (Green) in D2-Cre;Rosa26-YFP mice. Arrows show localization of Cre expression (YFP) in cholinergic neurons (CHT1 staining). Arrowheads show cholinergic neurons that do not express Cre. For additional brain regions, see <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001194#pbio.1001194.s001\" target=\"_blank\">Figure S1</a> and <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001194#pbio.1001194.s007\" target=\"_blank\">Table S1</a>.</p>", "links"=>[], "tags"=>["drives", "cre", "striatal", "cholinergic"], "article_id"=>385106, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_D2_Cre_drives_the_expression_of_Cre_in_striatal_cholinergic_neurons_/385106", "title"=>"D2-Cre drives the expression of Cre in striatal cholinergic neurons.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:25:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/714943"], "description"=>"<p>(a)VAChT mRNA expression, (b) ChAT mRNA expression, (c) CHT1 mRNA expression, (d) VAChT protein expression, (e) ChaT protein expression, (f) CHT1 protein expression, (g) representative immunoblot of control and VAChT<sup>D2-Cre-flox/flox</sup> striatal tissue, (h) VAChT protein expression in the hippocampus, and (i) representative immunoblot of protein expression in the hippocampus. ** <i>p</i><0.01 *** <i>p</i><0.001. mRNA expression levels were quantified by qPCR using actin to normalize the data, and figures represent <i>N</i> = 5 mice. Protein levels were quantified using synaptophysin as a loading control. <i>N</i> = 5 mice. See <a href=\"http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1001194#pbio.1001194.s002\" target=\"_blank\">Figure S2</a> for VAChT levels in the spinal cord.</p>", "links"=>[], "tags"=>["vacht", "striatum"], "article_id"=>385289, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_VAChT_in_the_striatum_of_VAChT_D2_Cre_flox_flox_mice_/385289", "title"=>"Expression of VAChT in the striatum of VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:28:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/715016"], "description"=>"<p>(a) Release of [<sup>3</sup>H]ACh from striatal slices in response to depolarization with KCl (33 mM). Basal release was subtracted from stimulated release to obtain only evoked release. *** <i>p</i><0.001. (b) Release of [<sup>3</sup>H]ACh from hippocampal slices performed as in (a). (c) Release of glutamate from striatal isolated nerve terminals and (d) expression of VGLUT 3 in the striatum. <i>N</i> = 5.</p>", "links"=>[], "tags"=>["acetylcholine", "glutamate"], "article_id"=>385366, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Release_of_acetylcholine_and_glutamate_from_VAChT_D2_Cre_flox_flox_mice_/385366", "title"=>"Release of acetylcholine and glutamate from VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:29:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/715091"], "description"=>"<p>(a) Horizontal locomotor activity in an open-field for VAChT<sup>D2-Cre-flox/flox</sup> (<i>N</i> = 24) and control mice (<i>N</i> = 27). (b) Cumulative 2 h locomotion VAChT<sup>D2-Cre-flox/flox</sup> (<i>N</i> = 24) and control mice (<i>N</i> = 27) (c) dark cycle activity of VAChT<sup>D2-Cre-flox/flox</sup> (<i>N</i> = 16) and control mice (<i>N</i> = 15). (d) Total locomotion activity during the first initial hours of the dark-cycle. (e) Habituation in the open-field measured as cumulative 2 h locomotion for VAChT<sup>D2-Cre-flox/flox</sup> and control mice in 3 consecutive days. ** <i>p</i><0.01, *** <i>p</i><0.001 compared to the first day. VAChT<sup>D2-Cre-flox/flox </sup><i>N</i> = 10; control mice <i>N</i> = 21.</p>", "links"=>[], "tags"=>["Mental health", "physiology", "neuroscience"], "article_id"=>385441, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Locomotor_activity_of_VAChT_D2_Cre_flox_flox_mice_/385441", "title"=>"Locomotor activity of VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:30:41"}
  • {"files"=>["https://ndownloader.figshare.com/files/715167"], "description"=>"<p>(a) Mice were injected with 5 mg/kg of cocaine after 20 min in the open-field and horizontal locomotor activity was measured. (b) Locomotor activity before and after injection of 20 mg/kg of cocaine. As with 5 mg/kg the mice were injected with cocaine after 20 min in the open-field. (c) Total locomotion during the 20 min following cocaine injection. ** <i>p</i><0.01. Injection of saline did not change locomotor activity for either genotype (unpublished data). For 5 mg/kg <i>N</i> = 7 for control and 9 for VAChT<sup>D2-Cre-flox/flox</sup>. For 20 mg/kg <i>N</i> = 10 for control and 15 for VAChT<sup>D2-Cre-flox/flox</sup> mice. For 40 mg/kg <i>N</i> = 8.</p>", "links"=>[], "tags"=>["locomotor"], "article_id"=>385520, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cocaine_mediated_locomotor_activity_in_VAChT_D2_Cre_flox_flox_mice_/385520", "title"=>"Cocaine-mediated locomotor activity in VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:32:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/715303"], "description"=>"<p>(a) In the conditioning phase (days 2–7) mice received alternating injections of 20 mg/kg of cocaine or vehicle and were immediately confined into one of the two conditioning chambers for 30 min. The CPP response was measured on day 8, when the animals were allowed to move freely in the CPP apparatus and the time spent in each compartment was measured (<i>N</i> = 6). (b) Reinstatement to cocaine was tested after extinction of CPP by pairing of the cocaine paired chamber with saline injections. Once the extinction was acquired, a prime of 10 mg/kg of cocaine was injected and the animals re-exposed to the CPP apparatus. The time spent in each compartment was measured (<i>N</i> = 5). * <i>p</i><0.05, reinstatement versus extinction. *** <i>p</i><0.001, cocaine paired versus saline paired.</p>", "links"=>[], "tags"=>["Mental health", "physiology", "neuroscience"], "article_id"=>385652, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CPP_response_of_VAChT_D2_Cre_flox_flox_mice_/385652", "title"=>"CPP response of VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:34:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/715365"], "description"=>"<p>(a) Repeated cocaine injections (10 mg/kg) promoted a progressive increase of locomotor sensitization (repeated measures ANOVAs show a significant effect of treatment, <i>F</i><sub>(1,16)</sub> = 33.855, <i>p</i><0.001). VAChT<sup>D2-Cre-flox/flox</sup> mice clearly manifested an enhancement in the locomotor activity in comparison with their control subjects (repeated measures ANOVAs show a significant effect of genotype, <i>F</i><sub>(1,16)</sub> = 4.902, * <i>p</i><0.05). (b) Cumulative 20 min locomotion after cocaine injection (10 mg/kg) of VAChT<sup>D2-Cre-flox/flox</sup> mice and controls (*** <i>p</i><0.001, day 6 versus day 1). Day 0 is the basal activity of the animals (no cocaine was injected).</p>", "links"=>[], "tags"=>["sensitization"], "article_id"=>385716, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g007"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Behavioural_sensitization_to_cocaine_/385716", "title"=>"Behavioural sensitization to cocaine.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:35:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/715439"], "description"=>"<p>(a) D1R mRNA expression in striatum, (b) D2R mRNA expression in striatum, (c) D2R mRNA expression in the midbrain, (d) M1 mRNA expression in striatum, (e) M2 mRNA expression in striatum, and (f) M4 mRNA expression in striatum. * <i>p</i><0.05 and ** <i>p</i><0.01.</p>", "links"=>[], "tags"=>["dopamine", "acetylcholine", "muscarinic", "receptors"], "article_id"=>385785, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g008"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Expression_of_dopamine_and_acetylcholine_muscarinic_receptors_in_VAChT_D2_Cre_flox_flox_mice_/385785", "title"=>"Expression of dopamine and acetylcholine muscarinic receptors in VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:36:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/715548"], "description"=>"<p>(a) Striatal D2R protein levels inVAChT<sup>D2-Cre-flox/flox</sup> mice and controls (<i>n</i> = 8). * <i>p</i><0.05. (b) D2R representative immunoblot blot. (c) Axial MRI FLASH image (500 μm thick) through the striatum (outlined region 1) and cerebral cortex (outlined region 2). (d) Average BOLD signal change in the striatum relative to cerebral cortex prior to and following injection of SFK 81297 at time zero (black arrow). Signal response for VAChT<sup>D2-Cre-flox/flox</sup> mice (<i>N</i> = 5) is shown with black triangles, and response for control mice (<i>N</i> = 4) is shown with open squares. Error bars represent the standard error of the mean. (e) Area under the curve for VAChT<sup>D2-Cre-flox/flox</sup> mice (<i>N</i> = 5) is shown with black triangles, and response for control mice (<i>N</i> = 4) is shown with open squares. The difference between genotypes was statistically significant (<i>p</i><0.01).</p>", "links"=>[], "tags"=>["dopamine", "receptor"], "article_id"=>385901, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g009"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Increased_dopamine_receptor_expression_and_activity_in_VAChT_D2_Cre_flox_flox_mice_/385901", "title"=>"Increased dopamine receptor expression and activity in VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:38:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/715646"], "description"=>"<p>(a) Effect of injection of SFK 81297 (3 mg/kg) 20 min after the mice were introduced to the open field, (b) dose-response for SKF 81297, (c) effect of quinpirole (0.01 mg/kg) as in (a), and (d) dose response for quinpirole. * <i>p</i><0.05, ** <i>p</i><0.01, and *** <i>p</i><0.001. <i>N</i> = 10 and 13 for saline, SKF 81297 <i>N</i> = 7 and 5 for 0.5 mg/kg, <i>N</i> = 9 and 4 for 3 mg/kg, and <i>N</i> = 7 and 9 for 8 mg/kg. For quinpirole <i>N</i> = 7 and 13 for 0.005 mg/kg, <i>N</i> = 17 and 15 for 0.01 mg/kg, <i>N</i> = 11 and 12 for 0.1 mg/kg, and <i>N</i> = 11 and 13 for 6 mg/kg for control and VAChT<sup>D2-Cre-flox/flox</sup> mice, respectively.</p>", "links"=>[], "tags"=>["d1r", "d2r", "agonists", "locomotor"], "article_id"=>385994, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.g010"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_D1R_or_D2R_agonists_on_locomotor_activity_in_VAChT_D2_Cre_flox_flox_mice_/385994", "title"=>"Effect of D1R or D2R agonists on locomotor activity in VAChT<sup>D2-Cre-flox/flox</sup> mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-11-08 01:39:54"}
  • {"files"=>["https://ndownloader.figshare.com/files/715781"], "description"=>"<p>HPLC analysis of supernatant samples of striatum from VAChT<sup>D2-Cre-flox/flox</sup> and control mice (<i>n</i> = 5). The samples were analyzed for norepinephrine (NE), dopamine (DA), and its two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) by NoAb BioDiscoveries. * <i>p</i><0.05.</p>", "links"=>[], "tags"=>["striatum", "mg"], "article_id"=>386130, "categories"=>["Physiology", "Neuroscience", "Mental Health"], "users"=>["Monica S. Guzman", "Xavier De Jaeger", "Sanda Raulic", "Ivana A. Souza", "Alex X. Li", "Susanne Schmid", "Ravi S. Menon", "Raul R. Gainetdinov", "Marc G. Caron", "Robert Bartha", "Vania F. Prado", "Marco A. M. Prado"], "doi"=>["https://dx.doi.org/10.1371/journal.pbio.1001194.t001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Catecholamine_content_in_the_striatum_ng_100_mg_of_brain_tissue_/386130", "title"=>"Catecholamine content in the striatum (ng/100 mg of brain tissue).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-11-08 01:42:10"}

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  • {"unique-ip"=>"28", "full-text"=>"11", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"24", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2019", "month"=>"12"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"7", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"8", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
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Relative Metric

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