Mapping Functional Brain Activation Using [14C]-Iodoantipyrine in Male Serotonin Transporter Knockout Mice
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{"title"=>"Mapping functional brain activation using [14C]-iodoantipyrine in male serotonin transporter knockout mice", "type"=>"journal", "authors"=>[{"first_name"=>"Raina D.", "last_name"=>"Pang", "scopus_author_id"=>"50262868000"}, {"first_name"=>"Zhuo", "last_name"=>"Wang", "scopus_author_id"=>"56042333600"}, {"first_name"=>"Lauren P.", "last_name"=>"Klosinski", "scopus_author_id"=>"50262286300"}, {"first_name"=>"Yumei", "last_name"=>"Guo", "scopus_author_id"=>"55788010400"}, {"first_name"=>"David H.", "last_name"=>"Herman", "scopus_author_id"=>"8780360700"}, {"first_name"=>"Tansu", "last_name"=>"Celikel", "scopus_author_id"=>"6603078168"}, {"first_name"=>"Hong Wei", "last_name"=>"Dong", "scopus_author_id"=>"57193262418"}, {"first_name"=>"Daniel P.", "last_name"=>"Holschneider", "scopus_author_id"=>"7004507398"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-80052005087", "sgr"=>"80052005087", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0023869", "pmid"=>"21886833", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"362405332"}, "id"=>"21b49adc-7736-3c03-bf81-487a8d41e957", "abstract"=>"BACKGROUND: Serotonin transporter knockout mice have been a powerful tool in understanding the role played by the serotonin transporter in modulating physiological function and behavior. However, little work has examined brain function in this mouse model. We tested the hypothesis that male knockout mice show exaggerated limbic activation during exposure to an emotional stressor, similar to human subjects with genetically reduced transcription of the serotonin transporter.\\n\\nMETHODOLOGY/PRINCIPAL FINDINGS: Functional brain mapping using [(14)C]-iodoantipyrine was performed during recall of a fear conditioned tone. Regional cerebral blood flow was analyzed by statistical parametric mapping from autoradiographs of the three-dimensionally reconstructed brains. During recall, knockout mice compared to wild-type mice showed increased freezing, increased regional cerebral blood flow of the amygdala, insula, and barrel field somatosensory cortex, decreased regional cerebral blood flow of the ventral hippocampus, and conditioning-dependent alterations in regional cerebral blood flow in the medial prefrontal cortex (prelimbic, infralimbic, and cingulate). Anxiety tests relying on sensorimotor exploration showed a small (open field) or paradoxical effect (marble burying) of loss of the serotonin transporter on anxiety behavior, which may reflect known abnormalities in the knockout animal's sensory system. Experiments evaluating whisker function showed that knockout mice displayed impaired whisker sensation in the spontaneous gap crossing task and appetitive gap cross training.\\n\\nCONCLUSIONS: This study is the first to demonstrate altered functional activation in the serotonin transporter knockout mice of critical nodes of the fear conditioning circuit. Alterations in whisker sensation and functional activation of barrel field somatosensory cortex extend earlier reports of barrel field abnormalities, which may confound behavioral measures relying on sensorimotor exploration.", "link"=>"http://www.mendeley.com/research/mapping-functional-brain-activation-using-14ciodoantipyrine-male-serotonin-transporter-knockout-mice-1", "reader_count"=>25, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>6, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>6, "Student > Bachelor"=>4, "Professor"=>2}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Agricultural and Biological Sciences"=>15, "Medicine and Dentistry"=>1, "Neuroscience"=>4, "Chemistry"=>1, "Psychology"=>1, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>4}, "Chemistry"=>{"Chemistry"=>1}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>15}, "Computer Science"=>{"Computer Science"=>2}}, "reader_count_by_country"=>{"Netherlands"=>2}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/743326"], "description"=>"<p>Depicted are select coronal slices (anterior-posterior coordinates relative to bregma) of the template brain. Colored overlays show statistically significant effects of genotype or conditioning or their interaction, but do not reflect the direction of the effect. Abbreviations are from Franklin and Paxinos mouse atlas <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone.0023869-Franklin1\" target=\"_blank\">[67]</a>: BL (basolateral amygdaloid nucleus), BM (basomedial amygdaloid nucleus), Ce (central amygdala), I (insular cortex), La (lateral amygdaloid nucleus), M1 (primary motor cortex), M2 (secondary motor cortex), MO (medial orbital cortex), PrL (prelimbic cortex), RS (retrosplenial cortex). Mouse brain atlas figures were reproduced from the mouse brain atlas <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone.0023869-Franklin1\" target=\"_blank\">[67]</a> with modification and with permission from Elsevier.</p>", "links"=>[], "tags"=>["examining", "conditioning"], "article_id"=>413694, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Factorial_analysis_examining_the_effect_of_genotype_conditioning_or_the_interaction_/413694", "title"=>"Factorial analysis examining the effect of genotype, conditioning or the interaction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:29:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/743169"], "description"=>"<p>5-HTT KO mice exhibit increased freezing specific to recall in a fear conditioning paradigm A) Training: WT and KO animals show similar freezing levels during training of fear conditioning. Time on the x-axis is labeled as ‘B’ for the entire two-minute baseline and each ‘T’ represents the thirty second tone and the following one-minute quiet period. The y-axis represents percent time freezing during the specific time point. B) Recall: KO mice compared to WT mice show significantly increased freezing during baseline and recall of a tone previously associated with foot shock. Time on the x-axis is represented in 30-second bins with ‘B’ for baseline and ‘T’ for tone exposure. The y-axis represents percent time freezing during the specific time bin. The arrow indicates time of radiotracer injection for the imaging data. Error bars represent standard error of the mean (shown only unilaterally for graphical clarity).</p>", "links"=>[], "tags"=>["neuroscience", "Biochemistry"], "article_id"=>413531, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g001", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Fear_Conditioning_/413531", "title"=>"Fear Conditioning.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:28:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/743560"], "description"=>"<p>A) 5-HTT KO mice show significantly decreased distance traveled throughout the arena in a novel open field. This is seen during the first 3 minutes of the test. B) KO mice show a non significant increase in latency to enter center zone C) There was no significant genotypic differences in number of entries into the center zone D) There was no significant genotypic difference in time spent in the center zone. Error bars represent standard error of the mean.</p>", "links"=>[], "tags"=>["neuroscience", "Biochemistry"], "article_id"=>413927, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Open_Field_/413927", "title"=>"Open Field.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:30:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/743450"], "description"=>"<p>Depicted are select coronal slices (anterior-posterior coordinates relative to bregma) of the template brain. Colored overlays show statistically significant increased (red) and decreased (blue) differences for each comparison. Intragroup comparison were examined for fear conditioning with respect to the different genotypes (WT: CF vs. CON and KO: CF vs. CON) and genotype effects with respect to conditioning (CF: KO vs. WT and CON: KO vs. WT). Abbreviations are from Franklin and Paxinos mouse atlas <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone.0023869-Franklin1\" target=\"_blank\">[67]</a>: Acb (accumbens nucleus), BL (basolateral amygdaloid nucleus), BM (basomedial amygdaloid nucleus), Cg (cingulate cortex), CPu (caudate putamen), DR (dorsal raphe nucleus), I (insular cortex), IC (inferior colliculus), La (lateral amygdaloid nucleus), M1 (primary motor cortex), M2 (secondary motor cortex), MnR (median raphe nucleus), MO (medial orbital cortex), PaS (parasubiculum), PrL (prelimbic cortex), RS (retrosplenial cortex), S1 (primary somatosensory cortex), S1BF (primary somatosensory, barrel field), S2 (secondary somatosensory cortex), ventral hippocampus (vHPC). Mouse brain atlas figures were reproduced from the mouse brain atlas <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone.0023869-Franklin1\" target=\"_blank\">[67]</a> with modification and with permission from Elsevier.</p>", "links"=>[], "tags"=>["mice", "conditioned"], "article_id"=>413822, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g003", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_functional_brain_activity_in_mice_in_response_to_a_fear_conditioned_tone_/413822", "title"=>"Changes in functional brain activity in mice in response to a fear conditioned tone.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:29:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/743959"], "description"=>"<p>Arrows (↑, ↓) indicate a positive or negative correlation of rCBF with the behavioral freezing score. Areas significant after correction for multiple comparisons are marked with an *p<0.05.</p>", "links"=>[], "tags"=>["rcbf", "freezing", "scores", "hemispheres"], "article_id"=>414321, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.t002", "stats"=>{"downloads"=>5, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Significant_correlation_of_rCBF_with_behavioral_freezing_scores_in_the_left_and_right_hemispheres_L_R_/414321", "title"=>"Significant correlation of rCBF with behavioral freezing scores in the left and right hemispheres (L/R).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 15:32:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/743836"], "description"=>"<p>a) Top: Schematic view of the experimental set-up. Animals tried to locate a target object (i.e. platform) placed after a gap <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone.0023869-Dubois1\" target=\"_blank\">[64]</a>. Their mobility is tracked using motion sensors. Bottom: Probability of successful object localization and subsequent gap-cross. 5-HTT deletion impairs tactile sensation (P<0.01, Kolmogorov-Smirnov test). b) Rewarded training for 3 weeks improves performance but does not rescue the whisker deficit. Top: Experimental set-up is similar to <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0023869#pone-0023869-g006\" target=\"_blank\">Figure 6a</a> with the addition of computer controlled reward delivery ports. Bottom: Probability of gap-crossing (WT vs KO, P<0.01, Kolmogorov-Smirnov test). c) Duration of exploration, i.e. time spent at the gap, d) time animals required to travel between the two ends of the platform during successful trials or the delay to return to the starting position after sensory exploration at the gap during failures, e) number of attempts (i.e. visits to the gap) f) duration of mobility across genotypes and training conditions. Please refer to the text for statistical comparisons. Error terms are standard errors of the means.</p>", "links"=>[], "tags"=>["whisker", "5-htt", "ko"], "article_id"=>414204, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g006", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impaired_whisker_function_in_5_HTT_KO_mice_/414204", "title"=>"Impaired whisker function in 5-HTT KO mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:31:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/743920"], "description"=>"<p>Arrows (↑<b>,</b> ↓) indicate the direction of rCBF change in the particular area and (-) indicates no significant change was noted. Areas significant after correction for multiple comparisons at the cluster level are marked with an *p<0.05. In addition, significance of the main effects of conditioning (CF) and genotype (KO), as well as their interaction on the ANOVA are noted as (#, p<0.05).</p>", "links"=>[], "tags"=>["changes", "rcbf", "cortex", "subcortex", "hemispheres"], "article_id"=>414282, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Significant_changes_in_rCBF_in_the_cortex_and_subcortex_in_the_left_and_right_hemispheres_L_R_/414282", "title"=>"Significant changes in rCBF in the cortex and subcortex in the left and right hemispheres (L/R).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-02-20 15:32:25"}
  • {"files"=>["https://ndownloader.figshare.com/files/743705"], "description"=>"<p>5-HTT KO mice compared to WT mice buried significantly less marbles placed in a novel cage; *p<0.001. Error bars represent standard error of the mean.</p>", "links"=>[], "tags"=>["neuroscience", "Biochemistry"], "article_id"=>414076, "categories"=>["Biochemistry", "Neuroscience"], "users"=>["Raina D. Pang", "Zhuo Wang", "Lauren P. Klosinski", "Yumei Guo", "David H. Herman", "Tansu Celikel", "Hong Wei Dong", "Daniel P. Holschneider"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0023869.g005", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Marble_Burying_/414076", "title"=>"Marble Burying.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 15:31:16"}

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