Enhanced NMDA Receptor-Mediated Modulation of Excitatory Neurotransmission in the Dorsal Vagal Complex of Streptozotocin-Treated, Chronically Hyperglycemic Mice
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{"title"=>"Enhanced NMDA receptor-mediated modulation of excitatory neurotransmission in the dorsal vagal complex of streptozotocin-treated, chronically hyperglycemic mice", "type"=>"journal", "authors"=>[{"first_name"=>"Eva C.", "last_name"=>"Bach", "scopus_author_id"=>"53879447500"}, {"first_name"=>"Katalin Cs", "last_name"=>"Halmos", "scopus_author_id"=>"7801499698"}, {"first_name"=>"Bret N.", "last_name"=>"Smith", "scopus_author_id"=>"35485984100"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84925763747", "sgr"=>"84925763747", "doi"=>"10.1371/journal.pone.0121022", "isbn"=>"1932-6203", "issn"=>"19326203", "pui"=>"603282302"}, "id"=>"9e5c9163-1fd5-3ae1-94b3-eb61217415d2", "abstract"=>"A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 micro M) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There was a greater relative effect of NMDA receptor antagonism in hyperglycemic mice, suggesting that augmented NMDA effects occur in neurons presynaptic to the DMV. Effects of NMDA receptor blockade on mEPSC frequency were equivalent in control and diabetic mice, suggesting that differential effects on glutamate release were due to altered NMDA function in the soma-dendritic membrane of intact afferent neurons. Application of NMDA (300 micro M) resulted in greater inward current and current density in NTS neurons recorded from hyperglycemic than control mice, particularly in glutamatergic NTS neurons identified by single-cell RT-PCR for VGLUT2. Overall expression of NR1 protein and message in the dorsal vagal complex were not different between the two groups. Enhanced postsynaptic NMDA responsiveness of glutamatergic NTS neurons is consistent with tonically-increased glutamate release in the DMV in mice with chronic hyperglycemia. Functional augmentation of NMDA-mediated responses may serve as a physiological counter-regulatory mechanism to control pathological disturbances of homeostatic autonomic function in type 1 diabetes.", "link"=>"http://www.mendeley.com/research/enhanced-nmda-receptormediated-modulation-excitatory-neurotransmission-dorsal-vagal-complex-streptoz", "reader_count"=>7, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>1, "Student > Bachelor"=>1, "Professor"=>1, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>1, "Neuroscience"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Japan"=>1, "Italy"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1982777"], "description"=>"<p><b>A.</b> Time course of plasma glucose concentration (± standard deviation) in control and STZ-treated mice. Numbers in parenthesis indicate the number of mice maintained up to each day post injection. <b>B.</b> Fluoro-Jade B staining in the dorsal vagal complex 24 h after intraperitoneal injection of saline (left) or STZ (200 mg/kg; right). Cellular Fluoro-Jade labeling, an indicator of necrotic cell death, was not observed in the vagal complex after peripheral STZ injection. AP, area postrema; NTS, nucleus tractus solitarius; DMV, dorsal motor nucleus of the vagus; cc, central canal; scale bar = 100 μm.</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351220, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g001", "stats"=>{"downloads"=>2, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_streptozotocin_STZ_injection_on_the_time_course_of_plasma_glucose_concentration_and_Fluoro_Jade_B_staining_in_the_dorsal_vagal_complex_/1351220", "title"=>"Effects of streptozotocin (STZ) injection on the time course of plasma glucose concentration and Fluoro-Jade B staining in the dorsal vagal complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982779"], "description"=>"<p><b>A.</b> Representative traces showing sEPSCs in DMV cells from control (left) and hyperglycemic (STZ; right) mice. <b>B.</b> Representative traces of mEPSCs in neurons from control (left) and hyperglycemic (STZ; right) mice. Arrows point to expanded sections of traces indicated in <b>A</b> and <b>B</b>; picrotoxin (100 μM) was present in all recordings. <b>C.</b> Group frequency and amplitude graphs for sEPSCs and mEPSCs in control and hyperglycemic (STZ) mice (asterisk indicates significant difference from control; p<0.05; Mann-Whitney U test; numbers of replicates are indicated above each bar).</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351222, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g002", "stats"=>{"downloads"=>0, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_sEPSCs_and_mEPSCs_in_dorsal_motor_nucleus_of_the_vagus_DMV_neurons_from_control_and_STZ_treated_hyperglycemic_mice_/1351222", "title"=>"Comparison of sEPSCs and mEPSCs in dorsal motor nucleus of the vagus (DMV) neurons from control and STZ-treated, hyperglycemic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982781"], "description"=>"<p><b>A.</b> Representative trace showing sEPSCs in a DMV neuron from a control mouse in control ACSF and during application of AP-5 (100 μM). <b>B.</b> Representative trace showing sEPSCs in a DMV neuron from a hyperglycemic mouse (STZ) before and during application of AP-5. Arrows point to expanded sections of traces indicated in <b>A</b> and <b>B</b>. <b>C.</b> Mean percent decrease in sEPSC frequency following application of AP-5 in control (n = 5) and hyperglycemic (n = 6) mice (asterisk indicates significant difference from control mice; p<0.05, Mann-Whitney U test). <b>D.</b> Mean percent decrease in mEPSC frequency following application of AP-5 in control (n = 9) and hyperglycemic (n = 10) mice. No difference was detected in the effect of AP-5 on mEPSC frequency in neurons from hyperglycemic and control mice (p = 0.97, Mann-Whitney U test).</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351224, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g003", "stats"=>{"downloads"=>1, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_AP_5_application_on_EPSCs_in_control_and_hyperglycemic_mice_/1351224", "title"=>"Effects of AP-5 application on EPSCs in control and hyperglycemic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982783"], "description"=>"<p><b>A.</b> Representative traces depicting whole cell current responses to application of NMDA (300 μM) in control and hyperglycemic mice (STZ). <b>B.</b> Average NMDA-mediated whole-cell current in control and hyperglycemic mice of the overall NTS neuron population sampled (n = 21 controls, n = 22 hyperglycemic), VGLUT2-positive neurons (VGLUT2+; n = 5 controls, n = 6 hyperglycemic) and VGLUT2-negative neurons (VGLUT2-; n = 4 controls, n = 5 hyperglycemic). * indicates significant difference from control (all cells; p<0.05; Mann-Whitney U test); # indicates significant difference from VGLUT2+ neurons in control mice (p<0.05; Mann-Whitney U test). <b>C.</b> Average NMDA-mediated current density in control and hyperglycemic conditions of VGLUT2+, and VGLUT2- NTS neuron populations. * indicates significant difference from NTS neurons from control mice (all cells; p<0.05); #, significant difference from control VGLUT2+ neurons (p<0.05). <b>D.</b> Examples of transcript detection using single-cell qRT-PCR for recorded VGLUT2+ and VLGUT2- neurons.</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351226, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g004", "stats"=>{"downloads"=>0, "page_views"=>32, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NMDA_mediated_whole_cell_current_amplitude_and_current_density_in_NTS_neurons_of_control_and_hyperglycemic_mice_/1351226", "title"=>"NMDA-mediated whole-cell current amplitude and current density in NTS neurons of control and hyperglycemic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982784"], "description"=>"<p><b>A.</b> NMDA (300 μM) mediated current-voltage responses in control (n = 12 at -80 to 0 mV; n = 7 at -80 to 30 mV) and hyperglycemic mice (STZ; n = 21 at -80 to 0 mV; n = 9 at -80 to 30 mV). Asterisk indicates significant difference from control (p<0.05; Mann-Whitney U test). <b>B.</b> Current-voltage responses confirming AP-5 sensitivity of NMDA-mediated current-voltage responses (n = 3; 2 control and 1 hyperglycemic).</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351227, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g005", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Current_voltage_response_relationships_in_NTS_neurons_from_control_and_hyperglycemic_mice_/1351227", "title"=>"Current-voltage response relationships in NTS neurons from control and hyperglycemic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/1982786"], "description"=>"<p><b>A.</b> Representative examples of NR1 subunit and β-actin protein expression in the dorsal vagal complex of control (n = 6) and hyperglycemic (STZ; n = 6) mice (bands to the left represent the protein ladder). <b>B.</b> Average NR1 protein expression in the dorsal vagal complex of control and hyperglycemic mice. <b>C.</b> NMDA receptor subunit mRNA abundance in control (n = 6) and hyperglycemic mice (n = 5), normalized to the three endogenous control genes β-actin, GAPDH and Hprt1.</p>", "links"=>[], "tags"=>["dorsal vagal", "glutamatergic NTS neurons", "Enhanced postsynaptic NMDA responsiveness", "glutamate release", "Chronically Hyperglycemic Mice", "dmv", "dorsal motor nucleus", "vglut", "Type 1 diabetes", "vagal motor neurons", "NMDA receptor blockade", "NMDA receptor antagonism", "NR 1 protein", "NMDA receptors", "ap", "Dorsal Vagal Complex"], "article_id"=>1351229, "categories"=>["Biological Sciences"], "users"=>["Eva C. Bach", "Katalin Cs. Halmos", "Bret N. Smith"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0121022.g006", "stats"=>{"downloads"=>0, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_NMDA_receptor_subunit_expression_in_control_and_hyperglycemic_mice_/1351229", "title"=>"NMDA receptor subunit expression in control and hyperglycemic mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-03-23 05:30:09"}

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{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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