An Active membrane model of the cerebellar Purkinje cellII: Simulation of synaptic responses. Schutter, E. D. & Bower, J. M. J. Neurophysiology, 71(1):401-419, 1994. abstract bibtex 1. A detailed compartmental model of a cerebellar Purkinje cell with active dendritic membrane was constructed. The model was based on anatomic reconstructions of single Purkinje cells and included 10 different types of voltage-dependent channels described by Hodgkin-Huxley equations, derived from Purkinje cell-specific voltage-clamp data where available. These channels included a fast and persistent Na+ channel, three voltage-dependent K+ channels, T-type and P-type Ca2+ channels, and two types of Ca2+-activated K+ channels. 2. The ionic channels were distributed differentially over three zones of the model, with Na+ channels in the soma, fast K+ channels in the soma and main dendrite, and Ca2+ channels and Ca2+-activated K+ channels in the entire dendrite. Channel densities in the model were varied until it could reproduce Purkinje cell responses to current injections in the soma or dendrite, as observed in slice recordings. 3. As in real Purkinje cells, the model generated two types of spiking behavior. In response to small current injections the model fired exclusively fast somatic spikes. These somatic spikes were caused by Na+ channels and repolarized by the delayed rectifier. When higher-amplitude current injections were given, sodium spiking increased in frequency until the model generated large dendritic Ca2+ spikes. Analysis of membrane currents underlying this behavior showed that these Ca2+ spikes were caused by the P-type Ca2+ channel and repolarized by the BK-type Ca2+-activated K+ channel. As in pharmacological blocking experiments, removal of Na+ channels abolished the fast spikes and removal of Ca2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior, the model also produced slow plateau potentials in both the dendrite and soma. These longer-duration potentials occurred in response to both short and prolonged current steps. Analysis of the model demonstrated that the plateau potentials in the soma were caused by the window current component of the fast Na+ current, which was much larger than the current through the persistent Na+ channels. Plateau potentials in the dendrite were carried by the same P-type Ca2+ channel that was also responsible for Ca2+ spike generation. The P channel could participate in both model functions because of the low-threshold K2-type Ca2+-activated K+ channel, which dynamically changed the threshold for dendritic spike generation through a negative feedback loop with the activation kinetics of the P-type Ca2+ channel. 5. These model responses were robust to changes in the densities of all of the ionic channels. For most of the channels, modifying their densities by factors of greater than or equal to 2 resulted only in left or right shifts of the frequency-current curve. However, changes of >20% to the amount of P-type Ca2+ channels or of one of the Ca2+-activated K+ channels in the model either suppressed dendritic spikes or caused the model to always fire Ca2+ spikes. Modeling results were also robust to variations in Purkinje cell morphology. We simulated models of two other anatomically reconstructed Purkinje cells with the same channel distributions and got similar responses to current injections. 6. The model was used to compare the electrotonic length of the Purkinje cell in the presence and absence of active dendritic conductances. The electrotonic distance from soma to the tip of the most distal dendrite increased from 0 57 lambda in a passive model to 0.95 lambda in a quiet model with active membrane. During a dendritic spike generated by current injection the distance increased even more, to 1.57 lambda. 7. Finally, the model was used to study the probable accuracy of experimental voltage-clamp data. Whole-cell patch-clamp conditions were simulated by blocking most of the K+ currents in the model. The increased electrotonic length due to the active dendritic membrane caused space clamp to fail, resulting in membrane potentials in proximal and distal dendrites that differed critically from the holding potential in the soma.
@article{ DeSchutter_Bower94b,
author = {De Schutter, E. and Bower, J. M.},
title = {An Active membrane model of the cerebellar {P}urkinje cell{II: S}imulation
of synaptic responses},
journal = {J. Neurophysiology},
year = {1994},
volume = {71},
pages = {401-419},
number = {1},
abstract = { 1. A detailed compartmental model of a cerebellar Purkinje cell with
active dendritic membrane was constructed. The model was based on
anatomic reconstructions of single Purkinje cells and included 10
different types of voltage-dependent channels described by Hodgkin-Huxley
equations, derived from Purkinje cell-specific voltage-clamp data
where available. These channels included a fast and persistent Na+
channel, three voltage-dependent K+ channels, T-type and P-type Ca2+
channels, and two types of Ca2+-activated K+ channels. 2. The ionic
channels were distributed differentially over three zones of the
model, with Na+ channels in the soma, fast K+ channels in the soma
and main dendrite, and Ca2+ channels and Ca2+-activated K+ channels
in the entire dendrite. Channel densities in the model were varied
until it could reproduce Purkinje cell responses to current injections
in the soma or dendrite, as observed in slice recordings. 3. As in
real Purkinje cells, the model generated two types of spiking behavior.
In response to small current injections the model fired exclusively
fast somatic spikes. These somatic spikes were caused by Na+ channels
and repolarized by the delayed rectifier. When higher-amplitude current
injections were given, sodium spiking increased in frequency until
the model generated large dendritic Ca2+ spikes. Analysis of membrane
currents underlying this behavior showed that these Ca2+ spikes were
caused by the P-type Ca2+ channel and repolarized by the BK-type
Ca2+-activated K+ channel. As in pharmacological blocking experiments,
removal of Na+ channels abolished the fast spikes and removal of
Ca2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior,
the model also produced slow plateau potentials in both the dendrite
and soma. These longer-duration potentials occurred in response to
both short and prolonged current steps. Analysis of the model demonstrated
that the plateau potentials in the soma were caused by the window
current component of the fast Na+ current, which was much larger
than the current through the persistent Na+ channels. Plateau potentials
in the dendrite were carried by the same P-type Ca2+ channel that
was also responsible for Ca2+ spike generation. The P channel could
participate in both model functions because of the low-threshold
K2-type Ca2+-activated K+ channel, which dynamically changed the
threshold for dendritic spike generation through a negative feedback
loop with the activation kinetics of the P-type Ca2+ channel. 5.
These model responses were robust to changes in the densities of
all of the ionic channels. For most of the channels, modifying their
densities by factors of greater than or equal to 2 resulted only
in left or right shifts of the frequency-current curve. However,
changes of >20% to the amount of P-type Ca2+ channels or of one of
the Ca2+-activated K+ channels in the model either suppressed dendritic
spikes or caused the model to always fire Ca2+ spikes. Modeling results
were also robust to variations in Purkinje cell morphology. We simulated
models of two other anatomically reconstructed Purkinje cells with
the same channel distributions and got similar responses to current
injections. 6. The model was used to compare the electrotonic length
of the Purkinje cell in the presence and absence of active dendritic
conductances. The electrotonic distance from soma to the tip of the
most distal dendrite increased from 0 57 lambda in a passive model
to 0.95 lambda in a quiet model with active membrane. During a dendritic
spike generated by current injection the distance increased even
more, to 1.57 lambda. 7. Finally, the model was used to study the
probable accuracy of experimental voltage-clamp data. Whole-cell
patch-clamp conditions were simulated by blocking most of the K+
currents in the model. The increased electrotonic length due to the
active dendritic membrane caused space clamp to fail, resulting in
membrane potentials in proximal and distal dendrites that differed
critically from the holding potential in the soma.},
en_number = {5.4:18}
}
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{"_id":"XLcXuLt9yR8if5FjK","bibbaseid":"schutter-bower-anactivemembranemodelofthecerebellarpurkinjecelliisimulationofsynapticresponses-1994","downloads":0,"creationDate":"2015-02-08T05:14:41.655Z","title":"An Active membrane model of the cerebellar Purkinje cellII: Simulation of synaptic responses","author_short":["Schutter, E.<nbsp>D.","Bower, J.<nbsp>M."],"year":1994,"bibtype":"article","biburl":"http://cnslab.mb.jhu.edu/niebase.bib","bibdata":{"abstract":"1. A detailed compartmental model of a cerebellar Purkinje cell with active dendritic membrane was constructed. The model was based on anatomic reconstructions of single Purkinje cells and included 10 different types of voltage-dependent channels described by Hodgkin-Huxley equations, derived from Purkinje cell-specific voltage-clamp data where available. These channels included a fast and persistent Na+ channel, three voltage-dependent K+ channels, T-type and P-type Ca2+ channels, and two types of Ca2+-activated K+ channels. 2. The ionic channels were distributed differentially over three zones of the model, with Na+ channels in the soma, fast K+ channels in the soma and main dendrite, and Ca2+ channels and Ca2+-activated K+ channels in the entire dendrite. Channel densities in the model were varied until it could reproduce Purkinje cell responses to current injections in the soma or dendrite, as observed in slice recordings. 3. As in real Purkinje cells, the model generated two types of spiking behavior. In response to small current injections the model fired exclusively fast somatic spikes. These somatic spikes were caused by Na+ channels and repolarized by the delayed rectifier. When higher-amplitude current injections were given, sodium spiking increased in frequency until the model generated large dendritic Ca2+ spikes. Analysis of membrane currents underlying this behavior showed that these Ca2+ spikes were caused by the P-type Ca2+ channel and repolarized by the BK-type Ca2+-activated K+ channel. As in pharmacological blocking experiments, removal of Na+ channels abolished the fast spikes and removal of Ca2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior, the model also produced slow plateau potentials in both the dendrite and soma. These longer-duration potentials occurred in response to both short and prolonged current steps. Analysis of the model demonstrated that the plateau potentials in the soma were caused by the window current component of the fast Na+ current, which was much larger than the current through the persistent Na+ channels. Plateau potentials in the dendrite were carried by the same P-type Ca2+ channel that was also responsible for Ca2+ spike generation. The P channel could participate in both model functions because of the low-threshold K2-type Ca2+-activated K+ channel, which dynamically changed the threshold for dendritic spike generation through a negative feedback loop with the activation kinetics of the P-type Ca2+ channel. 5. These model responses were robust to changes in the densities of all of the ionic channels. For most of the channels, modifying their densities by factors of greater than or equal to 2 resulted only in left or right shifts of the frequency-current curve. However, changes of >20% to the amount of P-type Ca2+ channels or of one of the Ca2+-activated K+ channels in the model either suppressed dendritic spikes or caused the model to always fire Ca2+ spikes. Modeling results were also robust to variations in Purkinje cell morphology. We simulated models of two other anatomically reconstructed Purkinje cells with the same channel distributions and got similar responses to current injections. 6. The model was used to compare the electrotonic length of the Purkinje cell in the presence and absence of active dendritic conductances. The electrotonic distance from soma to the tip of the most distal dendrite increased from 0 57 lambda in a passive model to 0.95 lambda in a quiet model with active membrane. During a dendritic spike generated by current injection the distance increased even more, to 1.57 lambda. 7. Finally, the model was used to study the probable accuracy of experimental voltage-clamp data. Whole-cell patch-clamp conditions were simulated by blocking most of the K+ currents in the model. The increased electrotonic length due to the active dendritic membrane caused space clamp to fail, resulting in membrane potentials in proximal and distal dendrites that differed critically from the holding potential in the soma.","author":["Schutter, E. De","Bower, J. M."],"author_short":["Schutter, E.<nbsp>D.","Bower, J.<nbsp>M."],"bibtex":"@article{ DeSchutter_Bower94b,\n author = {De Schutter, E. and Bower, J. M.},\n title = {An Active membrane model of the cerebellar {P}urkinje cell{II: S}imulation\n\tof synaptic responses},\n journal = {J. Neurophysiology},\n year = {1994},\n volume = {71},\n pages = {401-419},\n number = {1},\n abstract = { 1. A detailed compartmental model of a cerebellar Purkinje cell with\n\tactive dendritic membrane was constructed. The model was based on\n\tanatomic reconstructions of single Purkinje cells and included 10\n\tdifferent types of voltage-dependent channels described by Hodgkin-Huxley\n\tequations, derived from Purkinje cell-specific voltage-clamp data\n\twhere available. These channels included a fast and persistent Na+\n\tchannel, three voltage-dependent K+ channels, T-type and P-type Ca2+\n\tchannels, and two types of Ca2+-activated K+ channels. 2. The ionic\n\tchannels were distributed differentially over three zones of the\n\tmodel, with Na+ channels in the soma, fast K+ channels in the soma\n\tand main dendrite, and Ca2+ channels and Ca2+-activated K+ channels\n\tin the entire dendrite. Channel densities in the model were varied\n\tuntil it could reproduce Purkinje cell responses to current injections\n\tin the soma or dendrite, as observed in slice recordings. 3. As in\n\treal Purkinje cells, the model generated two types of spiking behavior.\n\tIn response to small current injections the model fired exclusively\n\tfast somatic spikes. These somatic spikes were caused by Na+ channels\n\tand repolarized by the delayed rectifier. When higher-amplitude current\n\tinjections were given, sodium spiking increased in frequency until\n\tthe model generated large dendritic Ca2+ spikes. Analysis of membrane\n\tcurrents underlying this behavior showed that these Ca2+ spikes were\n\tcaused by the P-type Ca2+ channel and repolarized by the BK-type\n\tCa2+-activated K+ channel. As in pharmacological blocking experiments,\n\tremoval of Na+ channels abolished the fast spikes and removal of\n\tCa2+ channels removed Ca2+ spiking. 4. In addition to spiking behavior,\n\tthe model also produced slow plateau potentials in both the dendrite\n\tand soma. These longer-duration potentials occurred in response to\n\tboth short and prolonged current steps. Analysis of the model demonstrated\n\tthat the plateau potentials in the soma were caused by the window\n\tcurrent component of the fast Na+ current, which was much larger\n\tthan the current through the persistent Na+ channels. Plateau potentials\n\tin the dendrite were carried by the same P-type Ca2+ channel that\n\twas also responsible for Ca2+ spike generation. The P channel could\n\tparticipate in both model functions because of the low-threshold\n\tK2-type Ca2+-activated K+ channel, which dynamically changed the\n\tthreshold for dendritic spike generation through a negative feedback\n\tloop with the activation kinetics of the P-type Ca2+ channel. 5.\n\tThese model responses were robust to changes in the densities of\n\tall of the ionic channels. For most of the channels, modifying their\n\tdensities by factors of greater than or equal to 2 resulted only\n\tin left or right shifts of the frequency-current curve. However,\n\tchanges of >20% to the amount of P-type Ca2+ channels or of one of\n\tthe Ca2+-activated K+ channels in the model either suppressed dendritic\n\tspikes or caused the model to always fire Ca2+ spikes. Modeling results\n\twere also robust to variations in Purkinje cell morphology. We simulated\n\tmodels of two other anatomically reconstructed Purkinje cells with\n\tthe same channel distributions and got similar responses to current\n\tinjections. 6. The model was used to compare the electrotonic length\n\tof the Purkinje cell in the presence and absence of active dendritic\n\tconductances. The electrotonic distance from soma to the tip of the\n\tmost distal dendrite increased from 0 57 lambda in a passive model\n\tto 0.95 lambda in a quiet model with active membrane. During a dendritic\n\tspike generated by current injection the distance increased even\n\tmore, to 1.57 lambda. 7. Finally, the model was used to study the\n\tprobable accuracy of experimental voltage-clamp data. Whole-cell\n\tpatch-clamp conditions were simulated by blocking most of the K+\n\tcurrents in the model. The increased electrotonic length due to the\n\tactive dendritic membrane caused space clamp to fail, resulting in\n\tmembrane potentials in proximal and distal dendrites that differed\n\tcritically from the holding potential in the soma.},\n en_number = {5.4:18}\n}","bibtype":"article","en_number":"5.4:18","id":"DeSchutter_Bower94b","journal":"J. Neurophysiology","key":"DeSchutter_Bower94b","number":"1","pages":"401-419","title":"An Active membrane model of the cerebellar Purkinje cellII: Simulation of synaptic responses","type":"article","volume":"71","year":"1994","bibbaseid":"schutter-bower-anactivemembranemodelofthecerebellarpurkinjecelliisimulationofsynapticresponses-1994","role":"author","urls":{},"downloads":0},"search_terms":["active","membrane","model","cerebellar","purkinje","cellii","simulation","synaptic","responses","schutter","bower"],"keywords":[],"authorIDs":[],"dataSources":["ErLXoH8mqSjESnrN5"]}