Multitarget pharmacology for Dystonia in M1 (Neymotin et al 2016)

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Accession:189154
" ... We developed a multiscale model of primary motor cortex, ranging from molecular, up to cellular, and network levels, containing 1715 compartmental model neurons with multiple ion channels and intracellular molecular dynamics. We wired the model based on electrophysiological data obtained from mouse motor cortex circuit mapping experiments. We used the model to reproduce patterns of heightened activity seen in dystonia by applying independent random variations in parameters to identify pathological parameter sets. ..."
Reference:
1 . Neymotin SA, Dura-Bernal S, Lakatos P, Sanger TD, Lytton WW (2016) Multitarget Multiscale Simulation for Pharmacological Treatment of Dystonia in Motor Cortex. Front Pharmacol 7:157 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Molecular Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex U1 pyramidal intratelencephalic L2-6 cell; Neocortex V1 interneuron basket PV cell; Neocortex fast spiking (FS) interneuron; Neocortex spiking regular (RS) neuron; Neocortex spiking low threshold (LTS) neuron; Neocortex layer 4 neuron; Neocortex layer 2-3 interneuron; Neocortex layer 4 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron;
Channel(s): I A; I h; I_SERCA; Ca pump; I K,Ca; I Calcium; I L high threshold; I T low threshold; I N; I_KD; I M; I Na,t;
Gap Junctions:
Receptor(s): GabaA; GabaB; AMPA; mGluR;
Gene(s): HCN1;
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Oscillations; Activity Patterns; Beta oscillations; Reaction-diffusion; Calcium dynamics; Pathophysiology; Multiscale;
Implementer(s): Neymotin, Sam [samn at neurosim.downstate.edu]; Dura-Bernal, Salvador [salvadordura at gmail.com];
Search NeuronDB for information about:  Neocortex V1 pyramidal corticothalamic L6 cell; Neocortex V1 interneuron basket PV cell; Neocortex U1 pyramidal intratelencephalic L2-6 cell; GabaA; GabaB; AMPA; mGluR; I Na,t; I L high threshold; I N; I T low threshold; I A; I M; I h; I K,Ca; I Calcium; I_SERCA; I_KD; Ca pump; Gaba; Glutamate;
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dystdemo
readme.txt
cagk.mod
cal.mod *
calts.mod *
can.mod *
cat.mod *
gabab.mod
h_winograd.mod
HCN1.mod
IC.mod *
icalts.mod *
ihlts.mod *
kap.mod
kcalts.mod *
kdmc.mod
kdr.mod
km.mod *
mglur.mod *
misc.mod *
MyExp2SynBB.mod *
MyExp2SynNMDABB.mod
nax.mod
stats.mod *
vecst.mod *
aux_fun.inc *
conf.py
declist.hoc *
decnqs.hoc *
decvec.hoc *
default.hoc *
drline.hoc *
geom.py
ghk.inc *
grvec.hoc
init.hoc
labels.hoc
labels.py *
local.hoc *
misc.h
mpisim.py
netcfg.cfg
nqs.hoc *
nqs.py
nrnoc.hoc *
pyinit.py *
python.hoc *
pywrap.hoc *
simctrl.hoc *
simdat.py
syn.py
syncode.hoc *
vector.py *
xgetargs.hoc *
                            
TITLE T-calcium channel
: T-type calcium channel
: MODELDB 126814 CA3 by Safiulina et al - http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=126814
: by Michele Migliore


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

	FARADAY = 96520 (coul)
	R = 8.3134 (joule/degC)
	KTOMV = .0853 (mV/degC)
}

PARAMETER {
	v (mV)
	celsius = 25	(degC)
	gcatbar=.003 (mho/cm2)
	cai = 50.e-6 (mM)
	cao = 2 (mM)
	q10 = 5
	mmin=0.2
	hmin=10
	a0h =0.015
	zetah = 3.5
	vhalfh = -75
	gmh=0.6	
	a0m =0.04
	zetam = 2
	vhalfm = -28
	gmm=0.1	
}


NEURON {
	SUFFIX cat
	USEION ca READ cai,cao WRITE ica
        RANGE gcatbar, ica, gcat
        RANGE hinf,minf,mtau,htau
}

STATE {
	m h 
}

ASSIGNED {
	ica (mA/cm2)
        gcat (mho/cm2)
	hinf
	htau
	minf
	mtau
}

INITIAL {
	rates(v)
	m = minf
	h = hinf
}

BREAKPOINT {
	SOLVE states METHOD cnexp
	gcat = gcatbar*m*m*h
	ica = gcat*ghk(v,cai,cao)

}

DERIVATIVE states {	: exact when v held constant
	rates(v)
	m' = (minf - m)/mtau
	h' = (hinf - h)/htau
}


FUNCTION ghk(v(mV), ci(mM), co(mM)) (mV) {
        LOCAL nu,f

        f = KTF(celsius)/2
        nu = v/f
        ghk=-f*(1. - (ci/co)*exp(nu))*efun(nu)
}

FUNCTION KTF(celsius (DegC)) (mV) {
        KTF = ((25./293.15)*(celsius + 273.15))
}


FUNCTION efun(z) {
	if (fabs(z) < 1e-4) {
		efun = 1 - z/2
	}else{
		efun = z/(exp(z) - 1)
	}
}

FUNCTION alph(v(mV)) {
  alph = exp(0.0378*zetah*(v-vhalfh)) 
}

FUNCTION beth(v(mV)) {
  beth = exp(0.0378*zetah*gmh*(v-vhalfh)) 
}

FUNCTION alpmt(v(mV)) {
  alpmt = exp(0.0378*zetam*(v-vhalfm)) 
}

FUNCTION betmt(v(mV)) {
  betmt = exp(0.0378*zetam*gmm*(v-vhalfm)) 
}

PROCEDURE rates(v (mV)) { :callable from hoc
	LOCAL a,b, qt
        qt=q10^((celsius-25)/10)

	a = 0.2*(-1.0*v+19.26)/(exp((-1.0*v+19.26)/10.0)-1.0)
	b = 0.009*exp(-v/22.03)
	minf = a/(a+b)
	mtau = betmt(v)/(qt*a0m*(1+alpmt(v)))
	if (mtau<mmin) {mtau=mmin}

	a = 1.e-6*exp(-v/16.26)
	b = 1/(exp((-v+29.79)/10.)+1.)
	hinf = a/(a+b)
	htau = beth(v)/(qt*a0h*(1+alph(v)))
	if (htau<hmin) {htau=hmin}
}


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