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.
References:
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]
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 anomalous rectifier channel
COMMENT
:
: Anomalous Rectifier Ih - cation (Na/K) channel in thalamocortical neurons
:
: Kinetic model of calcium-induced shift in the activation of Ih channels.
: Model of Destexhe et al., Biophys J. 65: 1538-1552, 1993, based on the
: voltage-clamp data on the calcium dependence of If in heart cells
: (Harigawa & Irisawa, J. Physiol. 409: 121, 1989)
:
: The voltage-dependence is derived from Huguenard & McCormick, 
: J Neurophysiol. 68: 1373-1383, 1992, based on voltage-clamp data of 
: McCormick & Pape, J. Physiol. 431: 291, 1990. 
:
: Modified model of the binding of calcium through a calcium-binding (CB)
: protein, which in turn acts on Ih channels.  This model was described in
: detail in the following reference:
:    Destexhe, A., Bal, T., McCormick, D.A. and Sejnowski, T.J.  Ionic 
:    mechanisms underlying synchronized oscillations and propagating waves
:    in a model of ferret thalamic slices. Journal of Neurophysiology 76:
:    2049-2070, 1996.
: See also http://www.cnl.salk.edu/~alain , http://cns.fmed.ulaval.ca
:
:   KINETIC MODEL:
:
:	  Normal voltage-dependent opening of Ih channels:
:
:		c1 (closed) <-> o1 (open)	; rate cst alpha(V),beta(V)
:
:	  Ca++ binding on CB protein
:
:		p0 (inactive) + nca Ca <-> p1 (active)	; rate cst k1,k2
:
:	  Binding of active CB protein on the open form (nexp binding sites) :
:
:		o1 (open) + nexp p1 <-> o2 (open)	; rate cst k3,k4
:
:
:   PARAMETERS:
:	It is more useful to reformulate the parameters k1,k2 into
:	k2 and cac = (k2/k1)^(1/nca) = half activation calcium dependence, 
:	and idem for k3,k4 into k4 and Pc = (k4/k3)^(1/nexp) = half activation
:	of Ih binding (this is like dealing with tau_m and m_inf instead of
:	alpha and beta in Hodgkin-Huxley equations)
:	- k2:	this rate constant is the inverse of the real time constant of 
:             	the binding of Ca to the CB protein
:	- cac:	the half activation (affinity) of the CB protein;
:		around 1 to 10 microM.  
:	- k4:	this rate constant is the inverse of the real time constant of 
:             	the binding of the CB protein to Ih channels
:		very low: it basically governs the interspindle period
:	- Pc:	the half activation (affinity) of the Ih channels for the
:		CB protein;
:	- nca:	number of binding sites of calcium on CB protein; usually 4
:	- nexp:	number of binding sites on Ih channels
:       - ginc: augmentation of conductance associated with the Ca bound state
:	  (about 2-3; see Harigawa & Hirisawa, 1989)
:
:
:   IMPORTANT REMARKS:
:       - This simple model for the binding of Ca++ on the open channel 
:	  suffies to account for the shift in the voltage-dependence of Ih
:	  activation with calcium (see details in Destexhe et al, 1993).
:	- It may be that calcium just binds to the Ih channel, preventing the 
:	  conformational change between open and closed; in this case one
:	  should take into account binding on the closed state, which is 
:	  neglected here.
:
:   MODIFICATIONS
:	- this file also contains a procedure ("activation") to estimate
:	  the steady-state activation of the current; callable from outside
:	- the time constant now contains a changeable minimal value (taum)
:	- shift: new local variable to displace the voltage-dependence
:	  (shift>0 -> depolarizing shift)
:
:
: Alain Destexhe, Salk Institute and Laval University, 1995
:
ENDCOMMENT

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

NEURON {
	SUFFIX iar
	USEION h READ eh WRITE ih VALENCE 1
	USEION ca READ cai
        RANGE ghbar, h_inf, tau_s, m, shift
	GLOBAL k2, cac, k4, Pc, nca, nexp, ginc, taum
}

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


PARAMETER {
	eh	= -40	(mV)
	celsius = 36	(degC)
	ghbar	= 2e-5 (mho/cm2)
	cac	= 0.002 (mM)		: half-activation of calcium dependence
	k2	= 0.0004 (1/ms)		: inverse of time constant
	Pc	= 0.01			: half-activation of CB protein dependence
	k4	= 0.001	(1/ms)		: backward binding on Ih
	nca	= 4			: number of binding sites of ca++
	nexp	= 1			: number of binding sites on Ih channels
	ginc	= 2			: augmentation of conductance with Ca++
	taum	= 20	(ms)		: min value of tau
	shift	= 0	(mV)		: shift of Ih voltage-dependence
}


STATE {
	c1	: closed state of channel
	o1	: open state
	o2	: CB-bound open state
	p0	: resting CB
	p1	: Ca++-bound CB
}


ASSIGNED {
	v	(mV)
	cai	(mM)
	ih	(mA/cm2)
        gh	(mho/cm2)
	h_inf
	tau_s	(ms)
	alpha	(1/ms)
	beta	(1/ms)
	k1ca	(1/ms)
	k3p	(1/ms)
	m
	tadj
}


BREAKPOINT {
	SOLVE ihkin METHOD sparse

	m = o1 + ginc * o2

	ih = ghbar * m * (v - eh)
}

KINETIC ihkin {
:
:  Here k1ca and k3p are recalculated at each call to evaluate_fct
:  because Ca or p1 have to be taken at some power and this does
:  not work with the KINETIC block.
:  So the kinetics is actually equivalent to
:	c1 <-> o1
:	p0 + nca Cai <-> p1
:	o1 + nexp p1 <-> o2

	evaluate_fct(v,cai)

	~ c1 <-> o1		(alpha,beta)

	~ p0 <-> p1		(k1ca,k2)

	~ o1 <-> o2		(k3p,k4)

	CONSERVE p0 + p1 = 1
	CONSERVE c1 + o1 + o2 = 1
}





INITIAL {
:
:  Experiments of McCormick & Pape were at 36 deg.C
:  Q10 is assumed equal to 3
:
        tadj = 3.0 ^ ((celsius-36 (degC) )/10 (degC) )

	evaluate_fct(v,cai)

	c1 = 1
	o1 = 0
	o2 = 0
	p0 = 1
	p1 = 0
}


UNITSOFF
PROCEDURE evaluate_fct(v (mV), cai (mM)) {

	h_inf = 1 / ( 1 + exp((v+75-shift)/5.5) )

	tau_s = (taum + 1000 / ( exp((v+71.5-shift)/14.2) + exp(-(v+89-shift)/11.6) ) ) / tadj

	alpha = h_inf / tau_s
	beta  = ( 1 - h_inf ) / tau_s

	k1ca = k2 * (cai/cac)^nca

	k3p = k4 * (p1/Pc)^nexp

}



:
:  procedure for evaluating the activation curve of Ih
:
PROCEDURE activation(v (mV), cai (mM)) { LOCAL cc

	evaluate_fct(v,cai)

	cc = 1 / (1 + (cac/cai)^nca ) 		: equil conc of CB-protein

	m = 1 / ( 1 + beta/alpha + (cc/Pc)^nexp )

	m = ( 1 + ginc * (cc/Pc)^nexp ) * m
}

UNITSON

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