Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model
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{"title"=>"Glutamate-Bound NMDARs Arising from In Vivo-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model", "type"=>"journal", "authors"=>[{"first_name"=>"Matteo", "last_name"=>"Farinella", "scopus_author_id"=>"36245162000"}, {"first_name"=>"Daniel T.", "last_name"=>"Ruedt", "scopus_author_id"=>"56178345100"}, {"first_name"=>"Padraig", "last_name"=>"Gleeson", "scopus_author_id"=>"16202455700"}, {"first_name"=>"Frederic", "last_name"=>"Lanore", "scopus_author_id"=>"26767988800"}, {"first_name"=>"R. Angus", "last_name"=>"Silver", "scopus_author_id"=>"7201936933"}], "year"=>2014, "source"=>"PLoS Computational Biology", "identifiers"=>{"scopus"=>"2-s2.0-84901358840", "sgr"=>"84901358840", "issn"=>"15537358", "doi"=>"10.1371/journal.pcbi.1003590", "pmid"=>"24763087", "isbn"=>"1553-7358 (Electronic) 1553-734X (Linking)", "pui"=>"373163016"}, "id"=>"612c5e9c-6d9b-39f6-906b-95e57174c096", "abstract"=>"In vivo, cortical pyramidal cells are bombarded by asynchronous synaptic input arising from ongoing network activity. However, little is known about how such 'background' synaptic input interacts with nonlinear dendritic mechanisms. We have modified an existing model of a layer 5 (L5) pyramidal cell to explore how dendritic integration in the apical dendritic tuft could be altered by the levels of network activity observed in vivo. Here we show that asynchronous background excitatory input increases neuronal gain and extends both temporal and spatial integration of stimulus-evoked synaptic input onto the dendritic tuft. Addition of fast and slow inhibitory synaptic conductances, with properties similar to those from dendritic targeting interneurons, that provided a 'balanced' background configuration, partially counteracted these effects, suggesting that inhibition can tune spatio-temporal integration in the tuft. Excitatory background input lowered the threshold for NMDA receptor-mediated dendritic spikes, extended their duration and increased the probability of additional regenerative events occurring in neighbouring branches. These effects were also observed in a passive model where all the non-synaptic voltage-gated conductances were removed. Our results show that glutamate-bound NMDA receptors arising from ongoing network activity can provide a powerful spatially distributed nonlinear dendritic conductance. This may enable L5 pyramidal cells to change their integrative properties as a function of local network activity, potentially allowing both clustered and spatially distributed synaptic inputs to be integrated over extended timescales.", "link"=>"http://www.mendeley.com/research/glutamatebound-nmdars-arising-vivolike-network-activity-extend-spatiotemporal-integration-l5-cortica", "reader_count"=>38, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>2, "Researcher"=>11, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Agricultural and Biological Sciences"=>20, "Medicine and Dentistry"=>2, "Neuroscience"=>12, "Physics and Astronomy"=>2, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Neuroscience"=>{"Neuroscience"=>12}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>20}, "Computer Science"=>{"Computer Science"=>2}}, "reader_count_by_country"=>{"United States"=>1, "Norway"=>1, "United Kingdom"=>1, "Spain"=>1}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1473915"], "description"=>"<p>(<b>A1–4</b>) Dendritic NMDAR spikes triggered in different terminal branches (30 synapses; 100 trials) in the absence (control) and presence of 900, 1200 and 1500 background excitatory synapses. Single trials (grey) and average (solid colour). (<b>B1</b>) Average NMDAR spikes in (A) overlaid. (<b>B2</b>) Average decay time (37% of peak) of NMDAR spikes in (A). (<b>C1</b>) Cumulative distributions of decay times for control and different levels of background input. (<b>C2</b>) NMDAR spike decay time distribution in the absence (black) and presence (blue) of 1500 background synapses. (<b>D</b>) Fractional increase in average NMDAR spike decay time for excitatory background synapses containing AMPAR/NMDARs (blue) and equivalent dendritic depolarization obtained with background AMPAR-only synapses (green) or current injection (red). (<b>E</b>) Cumulative distributions of NMDAR spike decay times during depolarization mediated by AMPAR-only (green) and mixed AMPAR/NMDAR (blue) background synaptic input.</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "extends", "duration", "nmdar"], "article_id"=>1006861, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g006", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_extends_the_duration_of_NMDAR_spikes_/1006861", "title"=>"Background excitatory input extends the duration of NMDAR spikes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473911"], "description"=>"<p>(<b>A</b>) Apical tuft with an example distribution of 60 synaptic inputs (red dots). (<b>B1</b>) Left: example voltage traces from all terminal apical branches (grey traces, N = 28) and the soma (red) in response to stimulation of 100 spatially distributed synaptic inputs at 200 Hz for 5 ms, during control conditions. Right: example trial for 100 ms stimulation window. (<b>B2</b>) Same as B1 in the presence of background activity from 1500 excitatory synapses. Somatic voltage traces are in blue and are truncated at +10 mV. (<b>C</b>) Probability of triggering action potentials (P(AP)) versus number of stimulated synapses, spatially distributed over the apical tuft. Synapses were driven with random trains with a window of 5 ms, 50 ms, 100 ms and 200 ms, and the frequency was scaled to maintain ∼1 quantal conductance per synapse, in the absence (red-yellow traces) and presence of background excitatory input (blue traces). (<b>D</b>) Number of distributed synapses required to trigger an AP with 50% probability (P(AP) = 0.5), for different levels of temporal dispersion in the stimulus evoked synapses (input window), in the absence (red) and presence of background excitatory input (blue), and during AMPAR-only background synaptic inputs which depolarized the dendrites to comparable levels (green).</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "enables", "spatially", "distributed", "synaptic", "temporal"], "article_id"=>1006857, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_enables_integration_of_spatially_distributed_synaptic_input_over_extended_temporal_windows_/1006857", "title"=>"Background excitatory input enables integration of spatially distributed synaptic input over extended temporal windows.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473909"], "description"=>"<p>(<b>A</b>) Somatic voltage response to the activation of 4 apical branches stimulated with 30 nearly synchronous synapses each, in the absence (black) and presence (blue) of 1500 background excitatory synapses distributed on the apical tuft. (<b>B</b>) Probability of triggering action potentials (P(AP)) versus number of stimulated branches, in the absence (black open circles) and presence of different levels of background excitation (blue filled circles). Lines show fits to a sigmoid function. Grey line and circles show results for 15 synaptic inputs per branch and 1500 background excitatory synapses.</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "synchronously", "stimulated", "branches"], "article_id"=>1006855, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_reduces_the_number_of_nearly_synchronously_stimulated_branches_required_to_trigger_action_potentials_/1006855", "title"=>"Background excitatory input reduces the number of nearly synchronously stimulated branches required to trigger action potentials.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473910"], "description"=>"<p>(<b>A1</b>) Left panel: example voltage traces in 4 terminal apical branches during near synchronous branch activation (5 ms window, 30 synapses per branch; grey traces) and from the soma (red). Other panels show responses when stimulated branches are desynchronized in progressively larger temporal windows (50 ms, 100 ms, 200 ms; soma traces lighter shades of orange). (<b>A2</b>) Same as A1 but during background input from 1500 excitatory synapses, for near-synchronous branch stimulation (5 ms; dark blue) or desynchronized in progressively larger temporal windows (50 ms, 100 ms, 200 ms; soma traces lighter shades of blue). (<b>B</b>) Probability of action potentials (P(AP)) versus number of stimulated apical branches for different degrees of temporal dispersion during background activity from 1500 background excitatory synapses (blue lines) compared to control condition (red-yellow lines). (<b>C</b>) Number of stimulated branches required to trigger an AP with 50% probability (P(AP) = 0.5), for different levels of temporal dispersion in the stimulated branches (input window), in the absence (red) and presence of background excitatory input (blue).</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "extends", "temporal", "stimulated"], "article_id"=>1006856, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_extends_the_temporal_integration_of_stimulated_branches_/1006856", "title"=>"Background excitatory input extends the temporal integration of stimulated branches.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473908"], "description"=>"<p>(<b>A</b>) Morphology of L5 pyramidal neuron model <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003590#pcbi.1003590-Larkum1\" target=\"_blank\">[29]</a> with apical tuft highlighted in blue. (<b>B</b>) The 28 terminal branches (red) on the dendritic tuft. (<b>C</b>) Membrane potential in an apical branch for different numbers of near-synchronous stimulated (5 ms window) quantal AMPAR/NMDAR synaptic inputs. Dashed line shows NMDAR spike threshold criterion (−30 mV). (<b>D</b>) Probability of NMDAR spike (P(NMDAR spike)) versus number of stimulated synapses randomly distributed along the branch. Red lines show fits for each of the 28 branches. Black line denotes average across all branches. (<b>E</b>) Membrane potential from a single branch during different levels of background excitatory input (exc, 900, 1200 and 1500 synapses firing at 0.85 Hz) distributed on the apical tuft (blue region in A). (<b>F</b>) Mean and standard deviation of branch voltage for different levels of background activity. (<b>G</b>) EPSP during control (black) and NMDAR spike during background excitatory input (blue) on the apical tuft. (<b>H</b>) Mean branch I-O relationship for 5 ms window (computed from ∼50 trials across randomly selected branches) during different levels of background input (as indicated). (<b>I</b>) Same as H but comparing results for a 5 ms stimulation window (filled circles, solid lines) and 15 ms window (open circles, dashed lines) for 1500 background inputs.</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "lowers", "nmdar", "spike", "input-output", "apical"], "article_id"=>1006854, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_lowers_NMDAR_spike_threshold_and_increases_gain_of_the_input_output_relationship_of_apical_dendrites_/1006854", "title"=>"Background excitatory input lowers NMDAR spike threshold and increases gain of the input-output relationship of apical dendrites.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473927"], "description"=>"<p>(<b>A</b>) Single trial of voltage response of apical branch triggered by nearly synchronous activation of 30 synapses (5 ms) during control (black), in presence of background activity from 1500 excitatory synapses (blue) and during mixed excitatory and inhibitory background (gGABA/gAMPA ratio of 1.5) provided by 130 pure GABA<sub>A</sub> receptor mediated synapses (2×SOM) firing at 3 Hz (red) or by a mixture of 65 SOM-like synapses and 13 NGF-like synapses providing both GABA<sub>A</sub> and GABA<sub>B</sub> receptor mediated inhibition firing at 14 Hz (SOM+NGF, green). (<b>B</b>) Cumulative distributions of NMDAR spike decay times for conditions in (A). (<b>C</b>) Additional branches activated during stimulation of a single branch for conditions in (A) (10 trials per branch, per condition).</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "inhibition", "modulates", "nmdar", "spike", "duration", "regeneration", "excitatory"], "article_id"=>1006873, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g009", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_inhibition_modulates_NMDAR_spike_duration_and_regeneration_during_background_excitatory_input_/1006873", "title"=>"Background inhibition modulates NMDAR spike duration and regeneration during background excitatory input.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473912"], "description"=>"<p>(<b>A</b>) Probability of an NMDAR spike (P(NMDAR spike)) occurring in a terminal branch versus number of nearly synchronous stimulus evoked synapses during control (black), in presence of background activity from 1500 excitatory synapses (blue) and during mixed excitatory and inhibitory background (gGABA/gAMPA ratio of 1.5) provided by 130 pure GABA<sub>A</sub> receptor (SOM-like) synapses firing random trains at 3 Hz (2×SOM, red) or by a combination of 65 SOM-like synapses and 13 NGF-like synapses providing both GABA<sub>A</sub> and GABA<sub>B</sub> receptor-mediated inhibition, firing random trains at 14 Hz (SOM+NGF, green). (<b>B1</b>) Example of voltages in 6 apical branches (grey) and soma (green) during nearly synchronous stimulation of 6 branches in the presence of ballanced background input (SOM+NGF). (<b>B2</b>) Example of voltages in all apical branches (grey) and soma (green) during nearly synchronous stimulation of 100 spatially distributed stimulus evokes synaptic inputs in the presence of balanced background input (SOM+NGF). (<b>C1</b>) Probability of triggering APs (P(AP)) versus number of nearly synchronously stimulated branches (5 ms, filled circles, solid lines) or asynchronously stimulated branches during a 100 ms window (open circles, dashed lines) for conditions in (A). (<b>C2</b>) Increase, from the nearly synchronous condition, in the number of stimulated branches required to trigger an AP (P(AP) = 0.5) with different levels of temporal dispersion (input) for conditions in (A) excluding control. (<b>D1</b>) P(AP) versus number of stimulated synapses for spatially distributed input over the apical tuft for conditions in (A). Synapses activated with random trains at 200 Hz for 5 ms (solid markers) or 10 Hz for 100 ms (empty markers). (<b>D2</b>) Number of spatially distributed synapses required to trigger an AP (P(AP) = 0.5) for different levels of temporal dispersion (input window), for conditions in (A).</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "inhibition", "modulates", "spatio-temporal"], "article_id"=>1006858, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g005", "stats"=>{"downloads"=>3, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_inhibition_modulates_spatio_temporal_integration_/1006858", "title"=>"Background inhibition modulates spatio-temporal integration.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473925"], "description"=>"<p>(<b>A</b>) Apical tuft with inset showing branch 11 (red) stimulated with 30 synaptic inputs (5 ms window) and branch 12 (blue) that receives no stimulus evoked input. Inset: enlarged tuft region with overlapping branches removed for clarity. (<b>B</b>) Membrane voltage of all 28 terminal apical branches during activation of branch 11 (red trace) in the presence (upper trace) and absence (lower trace) of distributed background synaptic activity from 900 excitatory inputs. Asterisks denote additional regenerative events triggered in branches 12 and 13 in the presence of background activity. (<b>C</b>) Voltage in branch 11 (red) and branch 12 (blue) with (solid lines) and without (dashed lines) background activity. (<b>D</b>) Average number of additional regenerative events triggered in neighbouring branches (identified using a 13 mV increase above level observed in the absence of background input) during different levels of background excitatory input (10 trials per branch, per condition).</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "dendritic", "triggers", "regenerative", "potentials", "neighbouring", "branches", "synaptic"], "article_id"=>1006871, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g007", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Stimulation_of_a_dendritic_branch_triggers_regenerative_potentials_in_neighbouring_branches_during_background_synaptic_input_/1006871", "title"=>"Stimulation of a dendritic branch triggers regenerative potentials in neighbouring branches during background synaptic input.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473926"], "description"=>"<p>(<b>A</b>) Probability of triggering an NMDAR spike (P(NMDAR spike)) in terminal branches versus number of nearly synchronous stimulated synapses in a passive model (solid lines), where all non-synaptic active dendritic conductances have been removed, in the absence (black) and presence of 1500 background excitatory synapses (blue). Original model shown for comparison (dashed lines). (<b>B</b>) NMDAR spike decay time distribution (N = 100, triggered with 30 synapses each) lines as for (A). Excitatory decay times distribution during control and during background activity. Inset, mean voltage (±SD) in randomly selected terminal branches (N = 100) with and without background activity in passive (filled symbols) and original model (open symbols). (<b>C</b>) Membrane voltage traces from all 28 terminal apical branches (as in <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003590#pcbi-1003590-g007\" target=\"_blank\"><b>Fig. 7</b></a>) in the passive model for a single trial, during nearly synchoronous activation of branch 11 (red traces) in the presence (upper trace; blue) and absence (lower trace; black) of background activity from 1500 excitatory inputs. Linear sum of the depolarization during control and during background input only, shown in green. (<b>D</b>) Peak depolarization induced by an NMDAR spike in branch 11 versus terminal branch number in absence (black) and presence (blue) of background activity. Peak depolarization during background activity alone shown in grey and peak value of linear sum of control during stimulation of branch 11 and background-only shown in green. (<b>E</b>) Voltage traces from branch 11 (red) and branch 7 (blue) in the absence (dashed lines) and presence of 1500 background excitatory inputs (solid lines). Grey and green trace as in (D). (<b>F</b>) Number of additional branches activated during background input when a single branch is stimulated (empty bar). This was estimated by stimulating the terminal branches in turn for 10 trials each and applying the 13 mV criterion, which identified regenerative peaks, although the number of branches exhibiting regenerative events is probably overestimated due to passive spread of voltage. Solid bar shows original model for comparison.</p>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "excitatory", "lowers", "extends", "duration", "regeneration", "nmdar", "spikes", "passive"], "article_id"=>1006872, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1003590.g008", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Background_excitatory_input_lowers_threshold_extends_duration_and_regeneration_of_NMDAR_spikes_in_a_passive_model_/1006872", "title"=>"Background excitatory input lowers threshold, extends duration and regeneration of NMDAR spikes in a passive model.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-04-24 03:13:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/1473948", "https://ndownloader.figshare.com/files/1473949", "https://ndownloader.figshare.com/files/1473950", "https://ndownloader.figshare.com/files/1473951", "https://ndownloader.figshare.com/files/1473952", "https://ndownloader.figshare.com/files/1473953", "https://ndownloader.figshare.com/files/1473954", "https://ndownloader.figshare.com/files/1473955", "https://ndownloader.figshare.com/files/1473956", "https://ndownloader.figshare.com/files/1473957", "https://ndownloader.figshare.com/files/1473958"], "description"=>"<div><p><i>In vivo</i>, cortical pyramidal cells are bombarded by asynchronous synaptic input arising from ongoing network activity. However, little is known about how such ‘background’ synaptic input interacts with nonlinear dendritic mechanisms. We have modified an existing model of a layer 5 (L5) pyramidal cell to explore how dendritic integration in the apical dendritic tuft could be altered by the levels of network activity observed <i>in vivo</i>. Here we show that asynchronous background excitatory input increases neuronal gain and extends both temporal and spatial integration of stimulus-evoked synaptic input onto the dendritic tuft. Addition of fast and slow inhibitory synaptic conductances, with properties similar to those from dendritic targeting interneurons, that provided a ‘balanced’ background configuration, partially counteracted these effects, suggesting that inhibition can tune spatio-temporal integration in the tuft. Excitatory background input lowered the threshold for NMDA receptor-mediated dendritic spikes, extended their duration and increased the probability of additional regenerative events occurring in neighbouring branches. These effects were also observed in a passive model where all the non-synaptic voltage-gated conductances were removed. Our results show that glutamate-bound NMDA receptors arising from ongoing network activity can provide a powerful spatially distributed nonlinear dendritic conductance. This may enable L5 pyramidal cells to change their integrative properties as a function of local network activity, potentially allowing both clustered and spatially distributed synaptic inputs to be integrated over extended timescales.</p></div>", "links"=>[], "tags"=>["Biochemistry", "Neurochemistry", "neurotransmitters", "glutamate", "Computational biology", "computational neuroscience", "Single neuron function", "neuroscience", "glutamate-bound", "nmdars", "arising", "spatio-temporal", "l5", "cortical", "pyramidal"], "article_id"=>1006889, "categories"=>["Biological Sciences"], "users"=>["Matteo Farinella", "Daniel T. Ruedt", "Padraig Gleeson", "Frederic Lanore", "R. Angus Silver"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1003590.s001", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s002", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s003", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s004", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s005", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s006", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s007", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s008", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s009", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s010", "https://dx.doi.org/10.1371/journal.pcbi.1003590.s011"], "stats"=>{"downloads"=>57, "page_views"=>49, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Glutamate_Bound_NMDARs_Arising_from_In_Vivo_like_Network_Activity_Extend_Spatio_temporal_Integration_in_a_L5_Cortical_Pyramidal_Cell_Model/1006889", "title"=>"Glutamate-Bound NMDARs Arising from <i>In Vivo</i>-like Network Activity Extend Spatio-temporal Integration in a L5 Cortical Pyramidal Cell Model", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-04-24 03:13:42"}

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