Synaptic and Intrinsic Activation of GABAergic Neurons in the Cardiorespiratory Brainstem Network
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{"title"=>"Synaptic and intrinsic activation of GABAergic neurons in the cardiorespiratory brainstem network", "type"=>"journal", "authors"=>[{"first_name"=>"Julie G.", "last_name"=>"Frank", "scopus_author_id"=>"56637157200"}, {"first_name"=>"David", "last_name"=>"Mendelowitz", "scopus_author_id"=>"7003593223"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pmid"=>"22570717", "pui"=>"364730463", "scopus"=>"2-s2.0-84860503843", "doi"=>"10.1371/journal.pone.0036459", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "sgr"=>"84860503843"}, "id"=>"97e189d1-044d-3b57-b89c-2e300f3c76d0", "abstract"=>"GABAergic pathways in the brainstem play an essential role in respiratory rhythmogenesis and interactions between the respiratory and cardiovascular neuronal control networks. However, little is known about the identity and function of these GABAergic inhibitory neurons and what determines their activity. In this study we have identified a population of GABAergic neurons in the ventrolateral medulla that receive increased excitatory post-synaptic potentials during inspiration, but also have spontaneous firing in the absence of synaptic input. Using transgenic mice that express GFP under the control of the Gad1 (GAD67) gene promoter, we determined that this population of GABAergic neurons is in close apposition to cardioinhibitory parasympathetic cardiac neurons in the nucleus ambiguus (NA). These neurons fire in synchronization with inspiratory activity. Although they receive excitatory glutamatergic synaptic inputs during inspiration, this excitatory neurotransmission was not altered by blocking nicotinic receptors, and many of these GABAergic neurons continue to fire after synaptic blockade. The spontaneous firing in these GABAergic neurons was not altered by the voltage-gated calcium channel blocker cadmium chloride that blocks both neurotransmission to these neurons and voltage-gated Ca(2+) currents, but spontaneous firing was diminished by riluzole, demonstrating a role of persistent sodium channels in the spontaneous firing in these cardiorespiratory GABAergic neurons that possess a pacemaker phenotype. The spontaneously firing GABAergic neurons identified in this study that increase their activity during inspiration would support respiratory rhythm generation if they acted primarily to inhibit post-inspiratory neurons and thereby release inspiration neurons to increase their activity. This population of inspiratory-modulated GABAergic neurons could also play a role in inhibiting neurons that are most active during expiration and provide a framework for respiratory sinus arrhythmia as there is an increase in heart rate during inspiration that occurs via inhibition of premotor parasympathetic cardioinhibitory neurons in the NA during inspiration.", "link"=>"http://www.mendeley.com/research/synaptic-intrinsic-activation-gabaergic-neurons-cardiorespiratory-brainstem-network", "reader_count"=>17, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>3, "Unspecified"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>3, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>2, "Student > Postgraduate"=>1, "Student > Bachelor"=>1, "Professor"=>3, "Unspecified"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>1, "Neuroscience"=>3, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>3}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Sweden"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/643246"], "description"=>"<p>a. In this confocal image, CVNs in the NA are labeled with rhodamine and are surrounded by smaller GABAergic cell bodies and terminals labeled with GFP. b. The 800 µm thick transverse medullary slice preparation from P3–P6 mice has all the necessary circuitry for respiratory rhythm generation including the preBötC, respiratory hypoglossal motorneurons and intact hypoglossal nerve rootlets, and the NA.</p>", "links"=>[], "tags"=>["gabaergic", "neurons", "proximity"], "article_id"=>313736, "categories"=>["Molecular Biology", "Biotechnology", "Neuroscience", "Cell Biology"], "users"=>["Julie G. Frank", "David Mendelowitz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036459.g001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Images_of_GABAergic_neurons_in_proximity_to_CVNs_/313736", "title"=>"Images of GABAergic neurons in proximity to CVNs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:36:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/643726"], "description"=>"<p>GABAergic neurons fire bursts of action potentials during XII bursts. Cells were patch clamped in the current clamp configuration with a small amount of current (<30 pA) injected to hold the cell at −65 mV. Inspiratory activity was measured from the hypoglossal rootlets (top two traces). Fewer than half of these cells (n = 8/20) continued to fire in the presence of CNQX and AP-5. In cells that showed continued activity, the synaptic activity to these neurons, as well as voltage gated calcium channels, were blocked by addition of cadmium chloride. Pacemaker activity patterns changed but frequencies between the three groups was not significantly different (Control: 1.7+/−0.4 Hz; CNQX & AP5: 1.7+/−0.5 Hz; CdCl<sub>2</sub>: 1.8+/−0.6 Hz).</p>", "links"=>[], "tags"=>["gabaergic", "pacemaker", "neurons", "altered", "blocked", "glutamatergic"], "article_id"=>314214, "categories"=>["Molecular Biology", "Biotechnology", "Neuroscience", "Cell Biology"], "users"=>["Julie G. Frank", "David Mendelowitz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036459.g004", "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Firing_in_GABAergic_pacemaker_neurons_is_altered_but_not_blocked_by_glutamatergic_antagonists_/314214", "title"=>"Firing in GABAergic pacemaker neurons is altered but not blocked by glutamatergic antagonists.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:38:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/643392"], "description"=>"<p>Glutamatergic receptors mediate excitatory neurotransmission to inspiratory GABAergic neurons. Inspiratory-related bursting activity was recorded from the hypoglossal rootlet (top trace) and electronically integrated (middle trace). Excitatory transmission to GABAergic neurons (bottom trace) was isolated by focal application of GABA (gabazine; 25 µM) and glycine (strychnine; 1 µM) receptor antagonists. Under control conditions there was a significant increase in EPSC frequency in the identified GABAergic neurons during inspiratory bursts control spontaneous: 3.5+/−0.5, control inspiratory: 12.6+/−1.9 Hz. DHßE (at concentrations of 1 µM, n = 8 and 100 µM, n = 7), and α-Btx (100 nM, n = 6) did not significantly change spontaneous or inspiratory related EPSC frequency. CNQX and AP5 blocked EPSC spontaneous and inspiratory frequency (p<0.05). The average results from all neurons tested (DHßE at 1 µM n = 8, at 100 µM n = 7, and with α-Btx at 100 nM, n = 6) are shown in the peri-inspiratory activity histogram, bottom, illustrating the average EPSC frequency (Hz) for each of the 5 seconds before the burst, frequency during the inspiratory burst (which typically lasted 1–2 seconds), and each of the 5 seconds following the inspiratory burst.</p>", "links"=>[], "tags"=>["gabaergic", "neurons", "glutamatergic", "blocked", "antagonists", "cnqx"], "article_id"=>313881, "categories"=>["Molecular Biology", "Biotechnology", "Neuroscience", "Cell Biology"], "users"=>["Julie G. Frank", "David Mendelowitz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036459.g002", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Respiratory_related_GABAergic_neurons_receive_glutamatergic_input_that_is_blocked_by_antagonists_CNQX_and_AP_5_/313881", "title"=>"Respiratory-related GABAergic neurons receive glutamatergic input that is blocked by antagonists CNQX and AP-5.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:37:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/643863"], "description"=>"<p>GABAergic neurons were patch clamped in the current clamp configuration. GABAergic neurons fire bursts of action potentials even in the presence of excitatory glutamatergic receptor blockers AP-5 and CNQX. However, application of 20 µM riluzole, the persistent sodium channel blocker nearly abolished all activity (p<0.05) (CNQX: 2.9+/−0.8 Hz; riluzole: 1.1+/−0.3, n = 6).</p>", "links"=>[], "tags"=>["pacemaker", "reduced", "persistent", "blocker"], "article_id"=>314354, "categories"=>["Molecular Biology", "Biotechnology", "Neuroscience", "Cell Biology"], "users"=>["Julie G. Frank", "David Mendelowitz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036459.g005", "stats"=>{"downloads"=>2, "page_views"=>23, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GABAergic_pacemaker_activity_is_reduced_by_the_persistent_sodium_current_blocker_riluzole_/314354", "title"=>"GABAergic pacemaker activity is reduced by the persistent sodium current blocker riluzole.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:39:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/643558"], "description"=>"<p>GABAergic neurons fire bursts of action potentials during inspiration. Cells were patch clamped in the current clamp configuration with a small amount of current when needed (<30 pA) injected to hold it at −65 mV. Inspiratory activity was measured from the hypoglossal rootlets (top two traces). Respiratory activity was greatly reduced in this population of cells. (Control: 1.7+/−0.4 Hz; CNQX & AP5: 0.2+/−0.3 Hz; p<0.05).</p>", "links"=>[], "tags"=>["inspiratory", "nonpacemaker", "cells", "bursts", "blocked", "cnqx"], "article_id"=>314047, "categories"=>["Molecular Biology", "Biotechnology", "Neuroscience", "Cell Biology"], "users"=>["Julie G. Frank", "David Mendelowitz"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0036459.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_GABAergic_inspiratory_nonpacemaker_cells_fire_in_bursts_that_are_blocked_by_CNQX_and_AP_5_/314047", "title"=>"GABAergic inspiratory nonpacemaker cells fire in bursts that are blocked by CNQX and AP-5.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 05:37:57"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"17", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"0", "cited-by"=>"2", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[308, 530, 649, 751, 844, 933, 1021, 1107, 1194, 1277, 1357, 1426, 1501, 1572, 1634, 1702, 1768, 1838, 1910, 1976, 2046, 2114, 2181, 2241, 2298]}, {"subject_area"=>"/Biology and life sciences/Biotechnology", "average_usage"=>[320, 560, 691, 804, 916, 1011, 1117, 1228, 1328, 1420, 1506, 1584, 1651, 1749, 1836, 1909, 1982, 2053, 2131, 2188, 2276, 2372, 2441, 2540, 2627]}, {"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[319, 556, 679, 785, 881, 970, 1062, 1149, 1236, 1323, 1402, 1474, 1545, 1617, 1681, 1754, 1822, 1892, 1963, 2031, 2099, 2165, 2233, 2299, 2359]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[325, 542, 658, 757, 836, 925, 1015, 1095, 1177, 1263, 1338, 1411, 1477, 1537, 1599, 1663, 1726, 1795, 1857, 1921, 1979, 2041, 2099, 2150, 2205]}, {"subject_area"=>"/Computer and information sciences", "average_usage"=>[352, 587, 696, 809, 901, 989, 1072, 1156, 1257, 1334, 1422, 1486, 1555, 1647, 1714, 1780, 1844, 1919, 1997, 2051, 2138, 2198, 2267, 2324, 2391]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[307, 529, 649, 751, 845, 936, 1025, 1113, 1197, 1284, 1360, 1432, 1501, 1570, 1632, 1697, 1765, 1834, 1904, 1972, 2041, 2107, 2170, 2231, 2292]}, {"subject_area"=>"/Medicine and health sciences/Medical devices and equipment", "average_usage"=>[241, 488, 601, 701, 777, 867, 943, 1011, 1074, 1140, 1183, 1219, 1283, 1338, 1408, 1471, 1600, 1656, 1718, 1766, 1836, 1906, 1985, 2041, 2105]}, {"subject_area"=>"/Medicine and health sciences/Physiology", "average_usage"=>[308, 535, 653, 754, 847, 930, 1020, 1103, 1188, 1268, 1351, 1420, 1487, 1550, 1614, 1679, 1757, 1830, 1898, 1961, 2024, 2086, 2150, 2216, 2266]}]}
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