Dendritic L-type Ca currents in motoneurons (Carlin et al 2000)

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Accession:19491
A component of recorded currents demonstrated kinetics consistent with a current originating at a site spatially segregated from the soma. In response to step commands this component was seen as a late-onset, low amplitude persistent current whilst in response to depolarizing-repolarizing ramp commands a low voltage clockwise current hysteresis was recorded. Simulations using a neuromorphic motoneuron model could reproduce these currents only if a noninactivating calcium conductance was placed in the dendritic compartments.
Reference:
1 . Carlin KP, Jones KE, Jiang Z, Jordan LM, Brownstone RM (2000) Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability. Eur J Neurosci 12:1635-46 [PubMed]
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Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s):
Channel(s): I L high threshold; I N; I Calcium;
Gap Junctions:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Bursting; Ion Channel Kinetics; Active Dendrites; Influence of Dendritic Geometry; Detailed Neuronal Models; Dendritic Bistability;
Implementer(s): Jones, Kelvin E [KEJones at ualberta.ca];
Search NeuronDB for information about:  I L high threshold; I N; I Calcium; 
AUTHOR: Kelvin E Jones, kejones@ualberta.ca
DATE: Dec 1, 2002

This collection of files can be used to reproduce the modeling results in:

K.P. Carlin, K.E. Jones, Z. Jiang, L.M. Jordan and R.M. Brownstone
Dendritic L-type calcium currents in mouse spinal motoneurons: implications for bistability.
European Journal of Neuroscience, Vol. 12, pp. 1635-1646, 2000

The parameters for the ion channels were adapted from:

V. Booth, J. Rinzel and O. Kiehn
Compartmental model of vertebrate motoneurons for Ca2+-dependent spiking and plateau potentials
under pharmacological treatment.
Journal of Neurophysiology, Vol. 78, pp. 3371-3385, 1997

The files are meant to reproduce the results illustrated in Figure 3 of Carlin et al. (2000).

The file fig_3aleft.hoc will produce the left panel of fig3a.  The file fig_3aright.hoc
needs to have the the fig_3aleft.hoc file run first.  These files produces approximations
to the figures in the paper.  If higher numerical resolution is desired the time step
can be decreased to 0.025 ms but of course this will take longer to calculate the figures.

If it is desired to indiviually generate these panels the following procedure may be followed:
In order to reproduce the various panels of the figure some editing will be needed.
All editing can be done in the file 'init.hoc' on the lines 11 & 17.
Line 11 opens the file describing the membrane mechanisms in the model, of which there are 7:

memb_N_soma.hoc, memb_N_dend.hoc, memb_LLVA_soma.hoc, memb_LLVA_dend.hoc, memb_LHVA_soma.hoc,
memb_LHVA_dend.hoc & memb_Lboth.hoc

Line 17 opens a session file for performing two types of experiments illustrated:

voltage_step.ses	//for doing the voltage step experiments of Fig 3A
ramp.ses		//for doing the ramp voltage clamp exp's of Figs 3B,C

In order to reproduce Fig 3A top, left panel (N type Ca2+ channels in soma):
Line 11= xopen("memb_N_soma.hoc")
Line 17= xopen("voltage_step.ses")

Fig 3A top, right panel (N type Ca2+ channels in dendrites):
Line 11= xopen("memb_N_dend.hoc")
Line 17= xopen("voltage_step.ses")


Prior to running the voltage_step.ses simulations:
1) Turn on 'Keep Lines' in the two Graph windows by right clicking and selecting *Keep Lines*
2) Click on VClamp in the PointProcess window and check the amplitude of the Testing Level.
   It can be left at -51 mV or depolarized to skip voltage test levels. Leave it odd though
   if you want to have figures like those publised.
3) Click on VClamp Family in the PointProcess window and make sure that there are about
   20 steps with a resolution of 2 mV/step.
4) Click on Quiet to suppress continuous drawing since these simulations take some time.
5) Click on Vary Test level in the PointProcess window to start the simulations.

On my machine with currents in the soma, the 700 ms voltage clamp protocol takes 17 sec Real Time.
With currents in the dendrites the same protocol takes 77 sec Real Time.

*/-----------------------------------------------------------------------------------------
// NOTE: The paper reports the currents as current density. This was done so that we could
// constrain the simulation to the experimental data. The model has an estimated capacitance
// of 8.4 nF using the same protocol as we used experimentally. The peak current density
// experimentally was 8.7 pA/pF where the capacitance of the cells was measured by integrating
// the current transient during a -10 mV, 50 ms voltage step and dividing by 10 mV.
-----------------------------------------------------------------------------------------*/


In order to reproduce Fig 3Bi (L_LVA type Ca2+ channels in soma):
Line 11= xopen("memb_LLVA_soma.hoc")
Line 17= xopen("ramp.ses")

Fig 3Bii (L_LVA type Ca2+ channels in dendrites):
Line 11= xopen("memb_LLVA_dend.hoc")
Line 17= xopen("ramp.ses")

Prior to running the ramp.ses simulations:
1) You will probably want to select Quiet to suppress the graph drawing to speed things up.
2) Check the parameters of the PointProcess by selecting R_VClamp: dur= 100, 20000, 100; amp= -120, -180, -120
3) Click on Init & Run and away you go.

On my machine these simulations with dendritic currents take >1800 sec (30 min). You don't get the I-V curve in
the paper but you can save the data and plot it that way if you like.