Differential Modulation of GABAA Receptors Underlies Postsynaptic Depolarization- and Purinoceptor-Mediated Enhancement of Cerebellar Inhibitory Transmission: A Non-Stationary Fluctuation Analysis Study
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{"title"=>"Differential modulation of gabaa receptors underlies postsynaptic depolarization-And purinoceptor-mediated enhancement of cerebellar inhibitory transmission: A non-stationary fluctuation analysis study", "type"=>"journal", "authors"=>[{"first_name"=>"Yumie", "last_name"=>"Ono", "scopus_author_id"=>"7402959957"}, {"first_name"=>"Fumihito", "last_name"=>"Saitow", "scopus_author_id"=>"6603646874"}, {"first_name"=>"Shiro", "last_name"=>"Konishi", "scopus_author_id"=>"7202506633"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"608995815", "doi"=>"10.1371/journal.pone.0150636", "issn"=>"19326203", "scopus"=>"2-s2.0-84962313242", "sgr"=>"84962313242"}, "id"=>"209cc548-86cc-3f97-a76c-e815466cc5ca", "abstract"=>"Cerebellar GABAergic inhibitory transmission between interneurons and Purkinje cells (PCs) undergoes a long-lasting enhancement following different stimulations, such as brief depolarization or activation of purinergic receptors of postsynaptic PCs. The underlying mechanisms, however, are not completely understood. Using a peak-scaled non-stationary fluctuation analysis, we therefore aimed at characterizing changes in the electrophysiological properties of GABAA receptors in PCs of rat cerebellar cortex during depolarization-induced \"rebound potentiation (RP)\" and purinoceptor-mediated long-term potentiation (PM-LTP), because both RP and PM-LTP likely depend on postsynaptic mechanisms. Stimulation-evoked inhibitory postsynaptic currents (eIPSCs) were recorded from PCs in neonatal rat cerebellar slices. Our analysis showed that postsynaptic membrane depolarization induced RP of eIPSCs in association with significant increase in the number of synaptic GABAA receptors without changing the channel conductance. By contrast, bath application of ATP induced PM-LTP of eIPSCs with a significant increase of the channel conductance of GABAA receptors without affecting the receptor number. Pretreatment with protein kinase A (PKA) inhibitors, H-89 and cAMPS-Rp, completely abolished the PM-LTP. The CaMKII inhibitor KN-62 reported to abolish RP did not alter PM-LTP. These results suggest that the signaling mechanism underlying PM-LTP could involve ATP-induced phosphorylation of synaptic GABAA receptors, thereby resulting in upregulation of the channel conductance by stimulating adenylyl cyclase-PKA signaling cascade, possibly via activation of P2Y11 purinoceptor. Thus, our findings reveal that postsynaptic GABAA receptors at the interneuron-PC inhibitory synapses are under the control of two distinct forms of long-term potentiation linked with different second messenger cascades.", "link"=>"http://www.mendeley.com/research/differential-modulation-gabaa-receptors-underlies-postsynaptic-depolarizationand-purinoceptormediate", "reader_count"=>9, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>5, "Student > Master"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Agricultural and Biological Sciences"=>2, "Neuroscience"=>6}, "reader_count_by_subdiscipline"=>{"Neuroscience"=>{"Neuroscience"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4800433"], "description"=>"<p>(A) PS-NSFA before and during RP. Upper panel: representative averaged traces of eIPSCs recorded before (thin line: Control) and after induction of RP (thick line: RP). Inset shows averaged trace of IPSCs recorded during the control period was scaled to the same amplitude of those recorded during RP (Normalized). Lower panel: representative plots of mean-variance curves before (control, open circles) and after induction of RP (closed circles). (B) PS-NSFA before and during PM-LTP. Upper panel: representative averaged traces of eIPSCs before (thin line: Control) and after application of ATP (thick line: ATP). Inset shows averaged trace of IPSCs recorded during the control period was scaled to the same amplitude of those recorded during PM-LTP induced by ATP (Normalized). Lower panel: representative plots of mean-variance curves before (control, open circles) and after induction of PM-LTP (closed circles). (C) Comparison of the mean value changes in the number of functioning GABA<sub>A</sub> receptors (<i>N</i>) and the size of unitary current through the GABA<sub>A</sub> receptor (<i>i</i>) during RP and ATP-induced PM-LTP. Asterisk indicates a statistically significant difference (p<0.01).</p>", "links"=>[], "tags"=>["eIPSC", "RP", "rat cerebellar cortex", "postsynaptic GABAA receptors", "PKA", "P 2Y purinoceptor", "potentiation", "rat cerebellar slices", "KN", "PC", "Cerebellar Inhibitory Transmission", "channel conductance", "ATP", "GABAA receptors", "synaptic GABAA receptors", "mechanism", "postsynaptic membrane depolarization", "GABAA Receptors Underlies Postsynaptic Depolarization"], "article_id"=>3087946, "categories"=>["Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Pharmacology", "Biotechnology", "Evolutionary Biology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Yumie Ono", "Fumihito Saitow", "Shiro Konishi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0150636.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Two_distinct_underlying_mechanisms_revealed_by_the_PS_NSFA_method_RP_and_PM_LTP_were_associated_with_increases_in_the_number_of_active_GABA_sub_A_sub_receptors_and_in_the_intensity_of_single_channel_conductance_respectively_/3087946", "title"=>"Two distinct underlying mechanisms revealed by the PS-NSFA method: RP and PM-LTP were associated with increases in the number of active GABA<sub>A</sub> receptors and in the intensity of single channel conductance, respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-03-01 06:52:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/4800262"], "description"=>"<p>(A) Effects of changing the driving force for GABA<sub>A</sub> receptor activation on eIPSCs. Upper panel: averaged traces of eIPSCs recorded at the holding membrane potential of –40 mV (thin line) and -60 mV (thick line). Inset shows the averaged trace of IPSCs recorded at −40 mV was scaled to the same amplitude of those recorded at –60 mV (Normalized). Lower panel: mean-variance curves at the membrane potentials of –40 (open circles) and –60 mV (closed circles). <i>N</i> and <i>i</i> indicate the number of active GABA<sub>A</sub> receptors and the size of unitary current through GABA<sub>A</sub> receptors estimated from the mean-variance curves, respectively. (B) Effects of changing the GABA<sub>A</sub> receptor availability by bicuculline on eIPSCs. Upper panel: averaged traces of eIPSCs before (control) and after bath-application of the GABA<sub>A</sub> receptor antagonist bicuculline (100 nM). Inset shows averaged trace of IPSCs in the presence of bicuculline was scaled to the same amplitude of those recorded in control solution (Normalized). Note that the decay time was prolonged after partial blockade of GABA<sub>A</sub> receptors by bicuculline. Lower panel: mean-variance curves before (open circles) and after (closed circles) application of bicuculline. <i>N</i> and <i>i</i> indicate the number of active GABA<sub>A</sub> receptors and the size of unitary current through the GABA<sub>A</sub> receptor estimated from the mean-variance curves, respectively.</p>", "links"=>[], "tags"=>["eIPSC", "RP", "rat cerebellar cortex", "postsynaptic GABAA receptors", "PKA", "P 2Y purinoceptor", "potentiation", "rat cerebellar slices", "KN", "PC", "Cerebellar Inhibitory Transmission", "channel conductance", "ATP", "GABAA receptors", "synaptic GABAA receptors", "mechanism", "postsynaptic membrane depolarization", "GABAA Receptors Underlies Postsynaptic Depolarization"], "article_id"=>3087820, "categories"=>["Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Pharmacology", "Biotechnology", "Evolutionary Biology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Yumie Ono", "Fumihito Saitow", "Shiro Konishi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0150636.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Validation_of_PS_NSFA_applied_to_eIPSCs_at_GABAergic_synapses_between_basket_cells_and_PCs_/3087820", "title"=>"Validation of PS-NSFA applied to eIPSCs at GABAergic synapses between basket cells and PCs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-03-01 06:52:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/4800520"], "description"=>"<p>(A, B,C) Time course change of the eIPSC amplitudes in experiments where ATP (100 μM) was applied after treatments with PKA inhibitors, H-89 (A) and cAMPS-Rp (B), and a CaMKII inhibitor, KN-62 (C). Inset shows representative averaged traces of eIPSC recorded before (thin line) and after ATP application (thick line). (D) Effects of PKA and CaMKII inhibitors on the mean amplitudes of eIPSCs recorded during the periods10 to 15 min after ATP application. (E) Effects PKA and CaMKII inhibitors on the mean values of changes in the number of functioning GABA<sub>A</sub> receptors (<i>N</i>) and the size of unitary current through the GABA<sub>A</sub> receptor (<i>i</i>). Filled bars (ATP) indicate the values obtained after application of ATP alone (data taken from Figs <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150636#pone.0150636.g002\" target=\"_blank\">2B</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0150636#pone.0150636.g003\" target=\"_blank\">3C</a>). Asterisk indicates a level of statistically significant difference (*: p<0.05, **: p<0.01, N.S.: no significant difference).</p>", "links"=>[], "tags"=>["eIPSC", "RP", "rat cerebellar cortex", "postsynaptic GABAA receptors", "PKA", "P 2Y purinoceptor", "potentiation", "rat cerebellar slices", "KN", "PC", "Cerebellar Inhibitory Transmission", "channel conductance", "ATP", "GABAA receptors", "synaptic GABAA receptors", "mechanism", "postsynaptic membrane depolarization", "GABAA Receptors Underlies Postsynaptic Depolarization"], "article_id"=>3088021, "categories"=>["Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Pharmacology", "Biotechnology", "Evolutionary Biology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Yumie Ono", "Fumihito Saitow", "Shiro Konishi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0150636.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Effects_of_PKA_and_CaMKII_inhibitors_on_PM_LTP_/3088021", "title"=>"Effects of PKA and CaMKII inhibitors on PM-LTP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-03-01 06:52:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/4800346"], "description"=>"<p>(A) Time course changes of eIPSC amplitude in the course of RP (n = 8, left panel) and PM-LTP (n = 6, right panel). RP was induced by depolarization pulses given to individual PCs at the time point indicated by an arrow. PM-LTP was induced by bath-application of 100 μM ATP during the period of 5 min indicated by a horizontal bar. (B) Mean amplitude of eIPSCs during the period of 10 to 15 min after induction of RP or PM-LTP. Asterisk indicates a statistically significant difference compared to mean amplitude of eIPSCs before induction of RP or PM-LTP (p<0.01).</p>", "links"=>[], "tags"=>["eIPSC", "RP", "rat cerebellar cortex", "postsynaptic GABAA receptors", "PKA", "P 2Y purinoceptor", "potentiation", "rat cerebellar slices", "KN", "PC", "Cerebellar Inhibitory Transmission", "channel conductance", "ATP", "GABAA receptors", "synaptic GABAA receptors", "mechanism", "postsynaptic membrane depolarization", "GABAA Receptors Underlies Postsynaptic Depolarization"], "article_id"=>3087886, "categories"=>["Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Pharmacology", "Biotechnology", "Evolutionary Biology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Yumie Ono", "Fumihito Saitow", "Shiro Konishi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0150636.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Rebound_potentiation_RP_and_purinoceptor_mediated_long_term_potentiation_PM_LTP_of_eIPSCs_at_basket_cell_PC_synapses_/3087886", "title"=>"Rebound potentiation (RP) and purinoceptor-mediated long-term potentiation (PM-LTP) of eIPSCs at basket cell-PC synapses.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-03-01 06:52:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/4800607"], "description"=>"<p>AC, adenylyl cyclase; CaM, Calmodulin; GABARAP, GABA<sub>A</sub> receptor-associated protein; P, phosphate.</p>", "links"=>[], "tags"=>["eIPSC", "RP", "rat cerebellar cortex", "postsynaptic GABAA receptors", "PKA", "P 2Y purinoceptor", "potentiation", "rat cerebellar slices", "KN", "PC", "Cerebellar Inhibitory Transmission", "channel conductance", "ATP", "GABAA receptors", "synaptic GABAA receptors", "mechanism", "postsynaptic membrane depolarization", "GABAA Receptors Underlies Postsynaptic Depolarization"], "article_id"=>3088093, "categories"=>["Biochemistry", "Cell Biology", "Genetics", "Molecular Biology", "Neuroscience", "Physiology", "Pharmacology", "Biotechnology", "Evolutionary Biology", "Developmental Biology", "Cancer", "Infectious Diseases"], "users"=>["Yumie Ono", "Fumihito Saitow", "Shiro Konishi"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0150636.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Schematic_representation_of_different_signaling_cascades_involved_in_the_mechanisms_underlying_RP_and_PM_LTP_/3088093", "title"=>"Schematic representation of different signaling cascades involved in the mechanisms underlying RP and PM-LTP.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2016-03-01 06:52:49"}

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Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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