Local Field Potential Modeling Predicts Dense Activation in Cerebellar Granule Cells Clusters under LTP and LTD Control
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{"title"=>"Local field potential modeling predicts dense activation in cerebellar granule cells clusters under LTP and LTD control", "type"=>"journal", "authors"=>[{"first_name"=>"Shyam", "last_name"=>"Diwakar", "scopus_author_id"=>"24511900300"}, {"first_name"=>"Paola", "last_name"=>"Lombardo", "scopus_author_id"=>"36883139800"}, {"first_name"=>"Sergio", "last_name"=>"Solinas", "scopus_author_id"=>"7003621167"}, {"first_name"=>"Giovanni", "last_name"=>"Naldi", "scopus_author_id"=>"6603876739"}, {"first_name"=>"Egidio", "last_name"=>"D'Angelo", "scopus_author_id"=>"7005399410"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-79960453750", "pmid"=>"21818278", "sgr"=>"79960453750", "doi"=>"10.1371/journal.pone.0021928", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "issn"=>"19326203", "pui"=>"362161317"}, "id"=>"13c399d3-8c75-3044-ba33-98f8c7e4d2ef", "abstract"=>"Local field-potentials (LFPs) are generated by neuronal ensembles and contain information about the activity of single neurons. Here, the LFPs of the cerebellar granular layer and their changes during long-term synaptic plasticity (LTP and LTD) were recorded in response to punctate facial stimulation in the rat in vivo. The LFP comprised a trigeminal (T) and a cortical (C) wave. T and C, which derived from independent granule cell clusters, co-varied during LTP and LTD. To extract information about the underlying cellular activities, the LFP was reconstructed using a repetitive convolution (ReConv) of the extracellular potential generated by a detailed multicompartmental model of the granule cell. The mossy fiber input patterns were determined using a Blind Source Separation (BSS) algorithm. The major component of the LFP was generated by the granule cell spike Na(+) current, which caused a powerful sink in the axon initial segment with the source located in the soma and dendrites. Reproducing the LFP changes observed during LTP and LTD required modifications in both release probability and intrinsic excitability at the mossy fiber-granule cells relay. Synaptic plasticity and Golgi cell feed-forward inhibition proved critical for controlling the percentage of active granule cells, which was 11% in standard conditions but ranged from 3% during LTD to 21% during LTP and raised over 50% when inhibition was reduced. The emerging picture is that of independent (but neighboring) trigeminal and cortical channels, in which synaptic plasticity and feed-forward inhibition effectively regulate the number of discharging granule cells and emitted spikes generating \"dense\" activity clusters in the cerebellar granular layer.", "link"=>"http://www.mendeley.com/research/local-field-potential-modeling-predicts-dense-activation-cerebellar-granule-cells-clusters-under-ltp", "reader_count"=>74, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>7, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>5, "Researcher"=>17, "Student > Doctoral Student"=>4, "Student > Ph. D. Student"=>22, "Student > Postgraduate"=>7, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>3, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Agricultural and Biological Sciences"=>30, "Business, Management and Accounting"=>1, "Computer Science"=>8, "Earth and Planetary Sciences"=>1, "Engineering"=>6, "Biochemistry, Genetics and Molecular Biology"=>1, "Materials Science"=>1, "Medicine and Dentistry"=>3, "Neuroscience"=>14, "Physics and Astronomy"=>4, "Psychology"=>1, "Social Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Social Sciences"=>{"Social Sciences"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>4}, "Psychology"=>{"Psychology"=>1}, "Unspecified"=>{"Unspecified"=>3}, "Engineering"=>{"Engineering"=>6}, "Neuroscience"=>{"Neuroscience"=>14}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>30}, "Computer Science"=>{"Computer Science"=>8}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"Greece"=>1, "United States"=>1, "Japan"=>2, "Italy"=>1, "United Kingdom"=>1, "France"=>1, "Germany"=>4, "India"=>3}, "group_count"=>3}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/755651"], "description"=>"<p>(<b>A</b>) Granule cell (GrC) responses generated by combining the input from 1 to 4 mossy fibers with inhibition from 0 to 4 Golgi cells (GoC). This gives rise to 20 fundamental combinations. Excitation and inhibition consist of a single pulse, with inhibition occurring 4 ms after the beginning of excitation. N<sub>2a</sub> is generated by the first and N<sub>2b</sub> by the second spike in a doublet. Schematics of the circuit are shown at the top. (<b>B</b>) The LFP <i>in vitro</i> is generated by jittered convolution of different responses in a 600 granule cell cluster, four of which are shown at the top. (<b>C</b>) The LFP control by synaptic receptors accounts for experimental observations: N<sub>2b</sub>, but not N<sub>2a</sub>, is increased by GABA-A receptor switch-off and reduced by subsequent NMDA receptor switch-off.</p>", "links"=>[], "tags"=>["Computational biology", "neuroscience"], "article_id"=>426021, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mechanism_of_local_field_potential_generation_in_vitro_/426021", "title"=>"Mechanism of local field potential generation <i>in vitro</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:40:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/756192"], "description"=>"<p>The field potential changes after TSS were recorded either in control conditions or with gabazine superfusion (t = 30 minutes after induction). Both T and C co-vary during LTD and LTP with gabazine.</p>", "links"=>[], "tags"=>["changes"], "article_id"=>426567, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Field_potential_changes_after_TSS_/426567", "title"=>"Field potential changes after TSS.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-19 01:49:27"}
  • {"files"=>["https://ndownloader.figshare.com/files/755395"], "description"=>"<p>(<b>A</b>) Schematic representation of a granule cell according to the model of Diwakar et al. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021928#pone.0021928-Diwakar1\" target=\"_blank\">[27]</a>. The granule cell generates synaptic responses in the dendritic endings and action potentials in the axon hillock. This forms two current sinks, with the axon hillock giving by far the major contribution. The broken arrows depict the current flow, colors indicate the major neuronal comportments. The Na<sup>+</sup> channels are concentrated in axon hillock, as indicated by immunohistochemistry <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021928#pone.0021928-Lu1\" target=\"_blank\">[43]</a>, the excitatory and inhibitory synaptic channels are located in the terminal dendritic compartments. The circuit schematics on the left shows the flow of transmembrane current over the extracellular resistance. The extracellular potentials generated by different compartments of the granule cell model are shown to the left (same colors as in the neuron compartments). Notice that the extracellular potential is the largest in correspondence of the hillock, where Na<sup>+</sup> channels have the highest density. (<b>B</b>) Extracellular field potential generated by a single granule cell “seen” from an electrode covering soma, dendrites and axon hillock (corresponding to a granular layer sink). Both in A and B, the neuron responds to the synchronous activation of all four mossy fibers (and all four inhibitory synapses, when active). Both in A and B, the neuron generates a single spike when synaptic inhibition is active, while it generates a doublet when synaptic inhibition is turned off.</p>", "links"=>[], "tags"=>["generated", "granule"], "article_id"=>425769, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Extracellular_field_potential_generated_by_a_single_granule_cell_/425769", "title"=>"Extracellular field potential generated by a single granule cell.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:36:09"}
  • {"files"=>["https://ndownloader.figshare.com/files/755778"], "description"=>"<p>(<b>A</b>) Different granule cell responses generated by combining the input from 1 to 4 mossy fibers with inhibition from 0 to 4 Golgi cells (GoC). Excitation consists of a pulse train at 500 Hz and inhibition of 1 impulse occurring 4 ms after the beginning of excitation. Due to redundancy, 4 out of 20 patterns (GrC/GrC = 1/4, 2/3, 3/2, 4/1; thicker lines) are sufficient to adequately reconstruct the LFP. The T and C waves are generated independently (C has a delay of 10 ms) and then summed linearly. Schematics of the circuit are shown at the top, illustrating independent circuits for T and C. (<b>B</b>) The LFP <i>in vitro</i> is generated by different combinations of responses, four of which are shown at the top. (<b>C</b>) The LFP control by synaptic receptors accounts for experimental observations: T and C are increased by GABA-A receptor switch-off and reduced by subsequent NMDA receptor switch-off.</p>", "links"=>[], "tags"=>["Computational biology", "neuroscience"], "article_id"=>426154, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mechanism_of_local_field_potential_generation_in_vivo_/426154", "title"=>"Mechanism of local field potential generation <i>in vivo</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:42:34"}
  • {"files"=>["https://ndownloader.figshare.com/files/756223"], "description"=>"<p>The table reports the relative percentage <i>w<sub>i</sub></i> of granule cells receiving 1 to 4 different mossy fibers (<i>N<sub>mf</sub></i>). The values used for simulation are approximations of those calculated by BSS. Note that the largest <i>w<sub>i</sub></i> error occurs for single connections, which make a minor contribution to the LFP.</p>", "links"=>[], "tags"=>["bss"], "article_id"=>426603, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.t001", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cross_validation_of_BSS_on_LFPs_/426603", "title"=>"Cross-validation of BSS on LFPs.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-19 01:50:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/379933"], "description"=>"<div><p>Local field-potentials (LFPs) are generated by neuronal ensembles and contain information about the activity of single neurons. Here, the LFPs of the cerebellar granular layer and their changes during long-term synaptic plasticity (LTP and LTD) were recorded in response to punctate facial stimulation in the rat in vivo. The LFP comprised a trigeminal (T) and a cortical (C) wave. T and C, which derived from independent granule cell clusters, co-varied during LTP and LTD. To extract information about the underlying cellular activities, the LFP was reconstructed using a repetitive convolution (ReConv) of the extracellular potential generated by a detailed multicompartmental model of the granule cell. The mossy fiber input patterns were determined using a Blind Source Separation (BSS) algorithm. The major component of the LFP was generated by the granule cell spike Na<sup>+</sup> current, which caused a powerful sink in the axon initial segment with the source located in the soma and dendrites. Reproducing the LFP changes observed during LTP and LTD required modifications in both release probability and intrinsic excitability at the mossy fiber-granule cells relay. Synaptic plasticity and Golgi cell feed-forward inhibition proved critical for controlling the percentage of active granule cells, which was 11% in standard conditions but ranged from 3% during LTD to 21% during LTP and raised over 50% when inhibition was reduced. The emerging picture is that of independent (but neighboring) trigeminal and cortical channels, in which synaptic plasticity and feed-forward inhibition effectively regulate the number of discharging granule cells and emitted spikes generating “dense” activity clusters in the cerebellar granular layer.</p> </div>", "links"=>[], "tags"=>["modeling", "activation", "cerebellar", "granule", "cells", "clusters", "ltp", "ltd"], "article_id"=>135085, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928", "stats"=>{"downloads"=>6, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Local_Field_Potential_Modeling_Predicts_Dense_Activation_in_Cerebellar_Granule_Cells_Clusters_under_LTP_and_LTD_Control/135085", "title"=>"Local Field Potential Modeling Predicts Dense Activation in Cerebellar Granule Cells Clusters under LTP and LTD Control", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2011-07-19 01:24:45"}
  • {"files"=>["https://ndownloader.figshare.com/files/755314"], "description"=>"<p>(<b>A</b>) LFPs recorded from Crus IIa before (black) and after the induction of plasticity with theta-sensory stimulation (16 air puffs at 4 Hz). <i>Left</i>, recording in control. <i>Right</i>, recording in the presence of gabazine. Each trace is the average of 20 responses. (<b>B</b>) Time-course of LFP variations for the peak T and C wave amplitudes measured relative to baseline before stimulation. The data are taken either in control (open symbols) and in the presence of gabazine (filled symbols). Note that LTP and LTD are similarly expressed both in the T and C wave. Data are reported as mean ± MSE (n = 5 in all series).</p>", "links"=>[], "tags"=>["ltd"], "article_id"=>425687, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LTP_and_LTD_of_the_T_and_C_waves_/425687", "title"=>"LTP and LTD of the T and C waves.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:34:47"}
  • {"files"=>["https://ndownloader.figshare.com/files/756106"], "description"=>"<p>(<b>A</b>) Simulated LFP changes <i>in vivo</i> obtained by changing release probability (<i>p</i>) alone (top) or together intrinsic excitability (IE) (bottom). The rising phase of the LFP is shown on expanded time-scale. (<b>B</b>) The plot shows the delay changes caused by <i>p</i> in T-wave. The three different curves represent levels of IE (low, normal and high). Note that appropriate LTP and LTD changes like those observed experimentally occur when both <i>p</i> and IE change bidirectionally around the control value. Each trace is the average of 15 simulations.</p>", "links"=>[], "tags"=>["synaptic", "plasticity"], "article_id"=>426479, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g008", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulations_of_the_effects_of_long_term_synaptic_plasticity_II_/426479", "title"=>"Simulations of the effects of long-term synaptic plasticity -II.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:47:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/755181"], "description"=>"<p>(<b>A</b>) On the <i>left</i>, a schematic representation of the somatosensory circuit: tr.n. = trigeminal nucleus; VB = ventro-basal thalamus; SI = primary somatosensory cortex (controlateral); a.p. = air-puff. On the <i>right</i>, two simultaneous recordings (black traces) from SI and Crus IIa are shown: the evoked field potentials were obtained by stimulating the same whisker pad region. In Crus-IIa, T is the first to appear. Note that SI precedes C and that SI inactivation with ice-cold extracellular Krebs solution leads to a selective and reversible reduction of C but not of T (grey trace) amplitude. These observations support the model in which T derives from the direct trigeminal pathway (blue), while C has a cortical origin (red). Each trace is the average of 20 responses. The inset shows the time-course of the cooling solution. (<b>B</b>) Responses recorded from an electrode positioned in Crus-IIa granular layer and elicited by moving the air-puff stimulus in different positions (the corresponding facial coordinates of the rat whiskers are shown in the inset). The changes in wave amplitude and shape indicate different receptive fields for each location. It should be noted that, in some cases, wave polarity is inverted while changing the stimulus position. Each trace is the average of 60 responses. The plot shows the amplitude of C relative to T peak (amplitude values are normalized to the average of the responses); data are obtained from 5 different experiments with stimulation in at least 4 different whisker-pad regions. The linear fit is C = 0.08+1.08T, with R<sup>2</sup> = 0.012. The T-C amplitude changes are therefore not correlated, indicating that two different clusters of granule cells are involved in generating T and C.</p>", "links"=>[], "tags"=>["waves", "trigeminal", "cortical"], "article_id"=>425556, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g001", "stats"=>{"downloads"=>3, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Origin_of_T_and_C_waves_from_trigeminal_and_cortical_pathways_/425556", "title"=>"Origin of T and C waves from trigeminal and cortical pathways.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:32:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/755504"], "description"=>"<p>(<b>A</b>) LFP simulating <i>in vitro</i> recordings in response to a single stimulus. The N<sub>2a</sub> and N<sub>2b</sub> waves are generated by a single cluster composed of 600 granule cells and are caused by spike doublets in granule cells in the absence of inhibition. The shape of the waveforms is expression of the temporal and spatial jittered convolution of several individual responses (cf. <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021928#pone-0021928-g003\" target=\"_blank\">Figure 3</a>). (<b>B</b>) LFP simulating <i>in vivo</i> recordings in response to a train of 3 stimuli at 300 Hz. The T and C waves are generated by different granule cell clusters with inhibition arriving 5 ms after the beginning of the stimulus. When both clusters surround the electrode, the two waves show negative polarity. However, C is inverted once the activated cluster moves proximally and the electrode records from axons. (<b>C</b>) The different time-scale of the response to a single stimulus and to bursts of stimuli is shown for comparison.</p>", "links"=>[], "tags"=>["reconstruction", "potentials", "repetitive"], "article_id"=>425879, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mathematical_reconstruction_of_local_field_potentials_by_repetitive_convolution_/425879", "title"=>"Mathematical reconstruction of local field potentials by repetitive convolution.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:37:59"}
  • {"files"=>["https://ndownloader.figshare.com/files/755925"], "description"=>"<p>(<b>A</b>) Simulated intracellular changes (top) and LFP changes (bottom) <i>in vivo</i> obtained by changing release probability (<i>p</i>) alone (left) or together intrinsic excitability (IE) (right). (<b>B</b>) The plots show the LFP T-wave and C-wave peak amplitude changes caused by release probability, <i>p</i>. The three different curves represent levels of IE (low, normal and high). Note that LTP and LTD changes similar to those observed experimentally occur when both <i>p</i> and IE change bidirectionally around the control value. Each trace is the average of 15 simulations.</p>", "links"=>[], "tags"=>["synaptic", "plasticity"], "article_id"=>426300, "categories"=>["Biological Sciences", "Neuroscience"], "users"=>["Shyam Diwakar", "Paola Lombardo", "Sergio Solinas", "Giovanni Naldi", "Egidio D'Angelo"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0021928.g007", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Simulations_of_the_effects_of_long_term_synaptic_plasticity_I_/426300", "title"=>"Simulations of the effects of long-term synaptic plasticity -I.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-07-19 01:45:00"}

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