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 L5/6 pyramidal GLU cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU cell; Neocortex V1 interneuron basket PV GABA 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 [Samuel.Neymotin at nki.rfmh.org]; Dura-Bernal, Salvador [salvadordura at gmail.com];
Search NeuronDB for information about:  Neocortex L5/6 pyramidal GLU cell; Neocortex V1 interneuron basket PV GABA cell; Neocortex U1 L2/6 pyramidal intratelencephalic GLU 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 Ca-dependent potassium current
:
:   Ca++ dependent K+ current IC responsible for 
:   action potentials AHP's
:   Differential equations
:
:   Model of Yamada, Koch & Adams, in: Methods in Neuronal Modeling,
:   Ed. by Koch & Segev, MIT press, 1989.
:
:   This current models the "fast" IK[Ca]:
:      - potassium current
:      - activated by intracellular calcium
:      - VOLTAGE DEPENDENT
:
:   Written by Alain Destexhe, Salk Institute, Sept 18, 1992
:
: should be considered 'BK' - fast, big conductance

NEURON {
	SUFFIX ikc
	USEION k READ ek WRITE ik
	USEION ca READ cai
        RANGE gkbar
	RANGE m_inf, tau_m
        RANGE taumin
        GLOBAL ascale,bscale,vfctr
}

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

PARAMETER {
	v		(mV)
        celsius         (degC)
	ek		(mV)
        cai             (mM)
	gkbar	= .003	(mho/cm2)	: taken from 
        taumin = 0.1
        ascale = 250.0
        bscale = 0.1
        vfctr = 24.0
}

STATE {
	m
}

INITIAL {
	evaluate_fct(v,cai)
	m = m_inf
}

ASSIGNED {
	ik	(mA/cm2)
	m_inf
	tau_m	(ms)
}

BREAKPOINT { 
	SOLVE states METHOD cnexp
	ik = gkbar * m * (v - ek)
}

DERIVATIVE states { 
	evaluate_fct(v,cai)
	m' = (m_inf - m) / tau_m
}

UNITSOFF
PROCEDURE evaluate_fct(v(mV),cai(mM)) {  LOCAL a,b,tadj
:
:  activation kinetics of Yamada et al were at 22 deg. C
:  transformation to 36 deg assuming Q10=3
:
	tadj = 3 ^ ((celsius-22.0)/10)

	a = ascale * cai * exp(v/vfctr)
	b = bscale * exp(-v/vfctr)

	tau_m = 1.0 / (a + b) / tadj
        if(tau_m < taumin){ tau_m = taumin }
	m_inf = a / (a + b)
}
UNITSON

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