Thalamocortical Relay cell under current clamp in high-conductance state (Zeldenrust et al 2018)

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Mammalian thalamocortical relay (TCR) neurons switch their firing activity between a tonic spiking and a bursting regime. In a combined experimental and computational study, we investigated the features in the input signal that single spikes and bursts in the output spike train represent and how this code is influenced by the membrane voltage state of the neuron. Identical frozen Gaussian noise current traces were injected into TCR neurons in rat brain slices to adjust, fine-tune and validate a three-compartment TCR model cell (Destexhe et al. 1998, accession number 279). Three currents were added: an h-current (Destexhe et al. 1993,1996, accession number 3343), a high-threshold calcium current and a calcium- activated potassium current (Huguenard & McCormick 1994, accession number 3808). The information content carried by the various types of events in the signal as well as by the whole signal was calculated. Bursts phase-lock to and transfer information at lower frequencies than single spikes. On depolarization the neuron transits smoothly from the predominantly bursting regime to a spiking regime, in which it is more sensitive to high-frequency fluctuations. Finally, the model was used to in the more realistic “high-conductance state” (Destexhe et al. 2001, accession number 8115), while being stimulated with a Poisson input (Brette et al. 2007, Vogels & Abbott 2005, accession number 83319), where fluctuations are caused by (synaptic) conductance changes instead of current injection. Under “standard” conditions bursts are difficult to initiate, given the high degree of inactivation of the T-type calcium current. Strong and/or precisely timed inhibitory currents were able to remove this inactivation.
1 . Zeldenrust F, Chameau P, Wadman WJ (2018) Spike and burst coding in thalamocortical relay cells. PLoS Comput Biol 14:e1005960 [PubMed]
2 . Destexhe A, Bal T, McCormick DA, Sejnowski TJ (1996) Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices. J Neurophysiol 76:2049-70 [PubMed]
3 . Huguenard JP, Mccormick DA (1994) Electrophysiology of the Neuron: An Interactive Tutorial
4 . Destexhe A, Rudolph M, Fellous JM, Sejnowski TJ (2001) Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons. Neuroscience 107:13-24 [PubMed]
5 . Brette R, Rudolph M, Carnevale T, Hines M, Beeman D, Bower JM, Diesmann M, Morrison A, Goodman PH, Harris FC, Zirpe M, Natschläger T, Pecevski D, Ermentrout B, Djurfeldt M, Lansner A, Rochel O, Vieville T, Muller E, Davison AP, El Boustani S, Destexhe A (2007) Simulation of networks of spiking neurons: a review of tools and strategies. J Comput Neurosci 23:349-98 [PubMed]
6 . Vogels TP, Abbott LF (2005) Signal propagation and logic gating in networks of integrate-and-fire neurons. J Neurosci 25:10786-95 [PubMed]
7 . Destexhe A, Neubig M, Ulrich D, Huguenard J (1998) Dendritic low-threshold calcium currents in thalamic relay cells. J Neurosci 18:3574-88 [PubMed]
8 . Destexhe A, Babloyantz A, Sejnowski TJ (1993) Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys J 65:1538-52 [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: Thalamus;
Cell Type(s): Thalamus geniculate nucleus/lateral principal GLU cell;
Channel(s): I L high threshold; I K,Ca; I h; I T low threshold;
Gap Junctions:
Simulation Environment: NEURON;
Model Concept(s): Bursting; Information transfer; Rebound firing; Sensory coding;
Implementer(s): Zeldenrust, Fleur [fleurzeldenrust at];
Search NeuronDB for information about:  Thalamus geniculate nucleus/lateral principal GLU cell; I L high threshold; I T low threshold; I h; I K,Ca;
cadecay.mod *
hh2.mod *
ic.mod *
Ih_des93.mod *
il.mod *
ITGHK.mod *
VClamp.mod *
El.oc *
loc3.oc *
stim_long.dat *
TITLE svclmp.mod


Single electrode Voltage clamp with three levels

Series Resistance added; backards compatible, except parameters 
e0,vo0,vi0,gain,rstim,tau1,tau2 that no longer exist

Clamp is on at time 0, and off at time dur[0]+dur[1]+dur[2]. When clamp is off
the injected current is 0.  The clamp levels are amp[0], amp[1], amp[2].  i is
the injected current, vc measures the control voltage) Do not insert several
instances of this model at the same location in order to make level changes.
That is equivalent to independent clamps and they will have incompatible
internal state values.

The electrical circuit for the clamp is exceedingly simple:

        rs           Rin
vc ---'\/\/`---o---'\/\/`---o
               |            |
               |____| |_____|
                    | |

Note that since this is an electrode current model v refers to the internal
potential which is equivalent to the membrane potential v when there is no
extracellular membrane mechanism present but is v+vext when one is present. 
Also since i is an electrode current, positive values of i depolarize the
cell. (Normally, positive membrane currents are outward and thus hyperpolarize
the cell)




        RANGE dur, amp, rs, vc, i

        (nA) = (nanoamp)
        (mV) = (millivolt)
        (uS) = (micromho)

        v (mV)
        rs = 1 (megohm)		: series resistance

        i (nA)
        vc (mV)
        ic (nA)
        tc2 (ms)
        tc3 (ms)
	dur[NSTEP] (ms)
	amp[NSTEP] (mV)

        tc2 = dur[0] + dur[1]
        tc3 = tc2 + dur[2]
        on = 0

        SOLVE vstim
        if (on) {
                i = (vc - v)/rs
                i = 0

PROCEDURE vstim() {
        on = 1
        if (t < dur[0]) {
                vc = amp[0]
        }else if (t < tc2) {
                vc = amp[1]
        }else if (t < tc3) {
                vc = amp[2]
        }else {
                vc = 0
                on = 0
        if (on) {
                ic = 0
        return 0;