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

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" ...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...."
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]
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;
Simulation Environment: NEURON;
Model Concept(s): Spindles; Oscillations;
Implementer(s): Knox, Andrew [knox at]; Destexhe, Alain [Destexhe at];
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;
cadecay.mod *
HH2.mod *
Ih.mod *
IT.mod *
IT2.mod *
kleak.mod *
vecevent.mod *
mosinit.hoc *

	One compartment model and currents derived from:

 	McCormick, D.A. and Huguenard, J.R.  A model of the 
	electrophysiological properties of thalamocortical relay neurons.  
	J. Neurophysiology 68: 1384-1400, 1992.

	- passive: parameters idem Rinzel
	- HH: Traub with higher threshold
	- IT: m2h, nernst, tau_h modified with double exponential
	- Ih: Huguenard with Ca++ dependence added, Ca++-binding protein
	- Ca++: simple decay, faster than McCormick

	This model is described in detail 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 ,

	Alain Destexhe, Salk Institute and Laval University, 1995


print " "
print " << defining template for one-compartment sTC cell >> "
print " "

begintemplate sTC		// create a new template object
public soma, kl, ampapost, gabaapost, gababpost, PYlist, TClist, REgabaalist, REgabablist

objectvar ampapost, gabaapost, gababpost, PYlist, TClist, REgabaalist, REgabablist

create soma[1]			// one compartment of about 29000 um2
soma {
  nseg = 1
  diam = 96
  L = 96
  cm = 1

objectvar kl

proc init() { local v_potassium, v_sodium

objectvar kl
kl = new kleak()

  v_potassium = -100		// potassium reversal potential 
  v_sodium = 50			// sodium reversal potential 

  soma {
	diam = 96		// geometry 
	L = 96			// so that area is about 29000 um2
	nseg = 1
	Ra = 100

	insert pas		// leak current 
	e_pas = -70		// original from Rinzel
	//e_pas = -100
	g_pas = 1e-5		//1e-5

	kl.loc(0.5)		// K-leak
	Erev_kleak = v_potassium
	kl.gmax = 0.004		// (uS)
				// conversion: x(uS) = x(mS/cm2)*29000e-8*1e3
				//		     = x(mS/cm2) * 0.29

	insert hh2		// Hodgin-Huxley INa and IK 
	ek = v_potassium
	ena = v_sodium
	vtraub_hh2 = -25	// High threshold to simulated IA
	gnabar_hh2 = 0.09  //original
	gkbar_hh2 = 0.01

	insert it		// T-current 
	cai = 2.4e-4 
	cao = 2 
	eca = 120 
	gcabar_it = 0.002 
	shift_it = 2

	insert iar		// h-current
	//eh = -40		// reversal
	eh = -40
	nca_iar = 4		// nb of binding sites for Ca++ on protein
	k2_iar = 0.0004		// decay of Ca++ binding on protein
	cac_iar = 0.002		// half-activation of Ca++ binding
	nexp_iar = 1		// nb of binding sites on Ih channel
	k4_iar = 0.001		// decay of protein binding on Ih channel
	Pc_iar = 0.01		// half-activation of binding on Ih channel
	ginc_iar = 2		// augm of conductance of bound Ih
	//ginc_iar = 1.25 		// augm of conductance of bound Ih
	ghbar_iar = 2e-5	// low Ih for slow oscillations

	insert cad		// calcium decay
	depth_cad = 1
	taur_cad = 5
	cainf_cad = 2.4e-4
	kt_cad = 0		// no pump

	PYlist = new List()
	TClist = new List()
	REgabaalist = new List()
	REgabablist = new List()

	ampapost = new AMPA_S(0.5)
	gabaapost = new GABAa_S(0.5)
	// ***Note: GABAb synapses are implemented as a list of individual synapses (in contrast to other synapse types), and so are created here
	gababpost = new List()


  print " "
  print "<< sTC: passive, Kleak, INa, IK, IT, Ih-CAM and Ca++ decay inserted >>"
  print " "

endtemplate sTC

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