Knox implementation of Destexhe 1998 spike and wave oscillation model (Knox et al 2018)

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Accession:234233
" ...The aim of this study was to use an established thalamocortical computer model to determine how T-type calcium channels work in concert with cortical excitability to contribute to pathogenesis and treatment response in CAE. METHODS: The model is comprised of cortical pyramidal, cortical inhibitory, thalamocortical relay, and thalamic reticular single-compartment neurons, implemented with Hodgkin-Huxley model ion channels and connected by AMPA, GABAA , and GABAB synapses. Network behavior was simulated for different combinations of T-type calcium channel conductance, inactivation time, steady state activation/inactivation shift, and cortical GABAA conductance. RESULTS: Decreasing cortical GABAA conductance and increasing T-type calcium channel conductance converted spindle to spike and wave oscillations; smaller changes were required if both were changed in concert. In contrast, left shift of steady state voltage activation/inactivation did not lead to spike and wave oscillations, whereas right shift reduced network propensity for oscillations of any type...."
Reference:
1 . Knox AT, Glauser T, Tenney J, Lytton WW, Holland K (2018) Modeling pathogenesis and treatment response in childhood absence epilepsy. Epilepsia 59:135-145 [PubMed]
Citations  Citation Browser
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network;
Brain Region(s)/Organism: Neocortex; Thalamus;
Cell Type(s): Thalamus reticular nucleus GABA cell; Thalamus geniculate nucleus/lateral principal GLU cell; Hodgkin-Huxley neuron; Neocortex layer 4 pyramidal cell; Neocortex fast spiking (FS) interneuron;
Channel(s): I h; I Na,t; I K,leak; I T low threshold; I M;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA;
Gene(s):
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Spindles; Oscillations;
Implementer(s): Knox, Andrew [knox at neurology.wisc.edu]; Destexhe, Alain [Destexhe at iaf.cnrs-gif.fr];
Search NeuronDB for information about:  Thalamus geniculate nucleus/lateral principal GLU cell; Thalamus reticular nucleus GABA cell; GabaA; GabaB; AMPA; I Na,t; I T low threshold; I K,leak; I M; I h;
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KnoxEtAl2017
README.html
README_.txt
ampa.mod
cadecay.mod *
gabaa.mod
gabab.mod
HH2.mod *
Ih.mod *
IM.mod
IT.mod *
IT2.mod *
ITREcustom.mod
kleak.mod *
vecevent.mod
Fsinglecell.oc
Fspikewave.oc
membrane_potential_heat_plot.py
mosinit.hoc *
RE.tem
rundemo.hoc
screenshot1.png
screenshot2.png
screenshot3.png
sIN.tem
sPY.tem
TC.tem
                            
TITLE Low threshold calcium current
:
:   Ca++ current responsible for low threshold spikes (LTS)
:   THALAMOCORTICAL CELLS
:   Differential equations
:
:   Model based on the data of Huguenard & McCormick, J Neurophysiol
:   68: 1373-1383, 1992 and Huguenard & Prince, J Neurosci.
:   12: 3804-3817, 1992.
:
:   Features:
:
:	- kinetics described by Nernst equations using a m2h format
:	- activation considered at steady-state
:	- inactivation fit to Huguenard's data using a bi-exp function
:	- shift for screening charge, q10 of inactivation of 3
:
:   Described in:
:    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
:   
:
:   Alain Destexhe, Salk Institute and Laval University, 1995
:

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

NEURON {
	SUFFIX it
	USEION ca READ cai,cao WRITE ica
	GLOBAL q10
	RANGE gcabar, m_inf, tau_m, h_inf, tau_h, shift
}

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

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

PARAMETER {
	v		(mV)
	celsius	= 36	(degC)
	gcabar	= 0.002	(mho/cm2)
	q10	= 3			: Q10 of inactivation
	shift	= 2 	(mV)		: corresponds to 2mM ext Ca++
	cai	= 2.4e-4 (mM)		: adjusted for eca=120 mV
	cao	= 2	(mM)
}

STATE {
	h
}

ASSIGNED {
	ica	(mA/cm2)
	carev	(mV)
	m_inf
	tau_m	(ms)			: dummy variable for compatibility
	h_inf
	tau_h	(ms)
	phi_h
}

BREAKPOINT {
	SOLVE castate METHOD cnexp
	carev = (1e3) * (R*(celsius+273.15))/(2*FARADAY) * log (cao/cai)
	ica = gcabar * m_inf * m_inf * h * (v-carev)
}

DERIVATIVE castate {
	evaluate_fct(v)

	h' = (h_inf - h) / tau_h
}


UNITSOFF
INITIAL {
:
:   Transformation to 36 deg assuming Q10 of 3 for h
:   (as in Coulter et al., J Physiol 414: 587, 1989)
:
	phi_h = q10 ^ ((celsius-24 (degC) )/10 (degC) )

	h = 0
}

PROCEDURE evaluate_fct(v(mV)) { LOCAL Vm

	Vm = v + shift

	m_inf = 1.0 / ( 1 + exp(-(Vm+57)/6.2) )
	h_inf = 1.0 / ( 1 + exp((Vm+81)/4.0) )

:	if(Vm < -80) {
:		tau_h = exp((Vm+467)/66.6) / phi_h
:	} else {
:		tau_h = ( 28 + exp(-(Vm+22)/10.5) ) / phi_h
:	}

	tau_h = 30.8 + (211.4 + exp((Vm+113.2)/5)) / (1 + exp((Vm+84)/3.2))

	tau_h = tau_h / phi_h

}

UNITSON