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

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Accession:232876
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.
Reference:
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]
Citations  Citation Browser
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:
Receptor(s):
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Bursting; Information transfer; Rebound firing; Sensory coding;
Implementer(s): Zeldenrust, Fleur [fleurzeldenrust at gmail.com];
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;
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TCR
current_clamp
cells
cadecay.mod *
hh2.mod *
ic.mod *
Ih_des93.mod *
il.mod *
ITGHK.mod *
VClamp.mod *
El.oc *
loc3.oc *
stim_long.dat *
tc3_cc_hcur_kc.hoc
                            
TITLE Low threshold calcium current
:
:   Ca++ current responsible for low threshold spikes (LTS)
:   Differential equations
:
:   Model of Huguenard & McCormick, J Neurophysiol 68: 1373-1383, 1992.
:   The kinetics is described by Goldman-Hodgkin-Katz equations,
:   using a m2h format, according to the voltage-clamp data
:   (whole cell patch clamp) of Huguenard & Prince, J. Neurosci. 
:   12: 3804-3817, 1992.
:
:   This model is described in detail in:
:   Destexhe A, Neubig M, Ulrich D and Huguenard JR.  
:   Dendritic low-threshold calcium currents in thalamic relay cells.  
:   Journal of Neuroscience 18: 3574-3588, 1998.
:   (a postscript version of this paper, including figures, is available on
:   the Internet at http://cns.fmed.ulaval.ca)
:
:    - shift parameter for screening charge
:    - empirical correction for contamination by inactivation (Huguenard)
:    - GHK equations
:
:
:   Written by Alain Destexhe, Laval University, 1995
:

INDEPENDENT {t FROM 0 TO 1 WITH 1 (ms)}

NEURON {
	SUFFIX itGHK
	USEION ca READ cai,cao WRITE ica
	RANGE pcabar, m_inf, tau_m, h_inf, tau_h, shift, actshift
	GLOBAL qm, qh
}

UNITS {
	(molar) = (1/liter)
	(mV) =	(millivolt)
	(mA) =	(milliamp)
	(mM) =	(millimolar)

	FARADAY = (faraday) (coulomb)
	R = (k-mole) (joule/degC)
}

PARAMETER {
	v		(mV)
	celsius	= 36	(degC)
	pcabar	=.2e-3	(cm/s)	: Maximum Permeability
	shift	= 2 	(mV)	: corresponds to 2mM ext Ca++
	actshift = 0 	(mV)	: shift of activation curve (towards hyperpol)
	cai	= 2.4e-4 (mM)	: adjusted for eca=120 mV
	cao	= 2	(mM)
	qm	= 5		: q10's for activation and inactivation
	qh	= 3		: from Coulter et al., J Physiol 414: 587, 1989
}

STATE {
	m h
}

ASSIGNED {
	ica	(mA/cm2)
	m_inf
	tau_m	(ms)
	h_inf
	tau_h	(ms)
	phi_m
	phi_h
}

BREAKPOINT {
	SOLVE castate METHOD euler
	ica = pcabar * m*m*h * ghk(v, cai, cao)
}

DERIVATIVE castate {
	evaluate_fct(v)

	m' = (m_inf - m) / tau_m
	h' = (h_inf - h) / tau_h
}


UNITSOFF
INITIAL {
	phi_m = qm ^ ((celsius-24)/10)
	phi_h = qh ^ ((celsius-24)/10)

	evaluate_fct(v)

	m = m_inf
	h = h_inf
}

PROCEDURE evaluate_fct(v(mV)) {
:
:   The kinetic functions are taken as described in the model of 
:   Huguenard & McCormick, and corresponds to a temperature of 23-25 deg.
:   Transformation to 36 deg assuming Q10 of 5 and 3 for m and h
:   (as in Coulter et al., J Physiol 414: 587, 1989).
:
:   The activation functions were estimated by John Huguenard.
:   The V_1/2 were of -57 and -81 in the vclamp simulations, 
:   and -60 and -84 in the current clamp simulations.
:
:   The activation function were empirically corrected in order to account
:   for the contamination of inactivation.  Therefore the simulations 
:   using these values reproduce more closely the voltage clamp experiments.
:   (cfr. Huguenard & McCormick, J Neurophysiol, 1992).
:
	m_inf = 1.0 / ( 1 + exp(-(v+shift+actshift+57)/6.2) )
	h_inf = 1.0 / ( 1 + exp((v+shift+81)/4.0) )

	tau_m = ( 0.612 + 1.0 / ( exp(-(v+shift+actshift+132)/16.7) + exp((v+shift+actshift+16.8)/18.2) ) ) / phi_m
	if( (v+shift) < -80) {
		tau_h = exp((v+shift+467)/66.6) / phi_h
	} else {
		tau_h = ( 28 + exp(-(v+shift+22)/10.5) ) / phi_h
	}
}

FUNCTION ghk(v(mV), ci(mM), co(mM)) (.001 coul/cm3) {
	LOCAL z, eci, eco
	z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
	eco = co*efun(z)
	eci = ci*efun(-z)
	:high cao charge moves inward
	:negative potential charge moves inward
	ghk = (.001)*2*FARADAY*(eci - eco)
}

FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}
FUNCTION nongat(v,cai,cao) {	: non gated current
	nongat = pcabar * ghk(v, cai, cao)
}
UNITSON