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

 Download zip file 
Help downloading and running models
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]
Citations  Citation Browser
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;
/
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 K-A channel from Klee Ficker and Heinemann
: modified to account for Dax A Current --- M.Migliore Jun 1997
: modified to be used with cvode  M.Migliore 2001
: thread-safe 2010-05-31 Ben Suter
: 2010-11-07 Ben Suter, removing "ka" from parameter names, reformatting, setting sh = 0 (was 24 mV)
:
: :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
: Copyright 2011, Benjamin Suter (for changes only)
: Used in model of corticospinal neuron BS0284 and published as:
:  "Intrinsic electrophysiology of mouse corticospinal neurons: a characteristic set of features embodied in a realistic computational model"
:  by Benjamin Suter, Michele Migliore, and Gordon Shepherd
:  Submitted September 2011
: :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::


UNITS {
    (mA) = (milliamp)
    (mV) = (millivolt)
}

PARAMETER {
    v                   (mV)
    celsius             (degC)
    ek

    sh      = 0
    gbar    = 0.008     (mho/cm2)
    vhalfn  = 11        (mV)
    vhalfl  = -56       (mV)
    a0l     = 0.05      (/ms)
    a0n     = 0.05      (/ms)
    zetan   = -1.5      (1)
    zetal   = 3         (1)
    gmn     = 0.55      (1)
    gml     = 1         (1)
    lmin    = 2         (mS)
    nmin    = 0.1       (mS)
    pw      = -1        (1)
    tq      = -40
    qq      = 5
    q10     = 5
    qtl     = 1
}


NEURON {
    SUFFIX kap
    USEION k READ ek WRITE ik
    RANGE gbar,g, sh
:        GLOBAL ninf,linf,taul,taun,lmin
}

STATE {
    n
    l
}

ASSIGNED {
    ik      (mA/cm2)
    ninf
    linf
    taul
    taun
    g
}

INITIAL {
    rates(v)
    n=ninf
    l=linf
}


BREAKPOINT {
    SOLVE states METHOD cnexp
    g = gbar*n*l
    ik = g*(v-ek)
}


FUNCTION alpn(v(mV)) {
    LOCAL zeta
    zeta=zetan+pw/(1+exp((v-tq-sh)/qq))
    alpn = exp(1.e-3*zeta*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius)))
}

FUNCTION betn(v(mV)) {
    LOCAL zeta
    zeta=zetan+pw/(1+exp((v-tq-sh)/qq))
    betn = exp(1.e-3*zeta*gmn*(v-vhalfn-sh)*9.648e4/(8.315*(273.16+celsius)))
}

FUNCTION alpl(v(mV)) {
    alpl = exp(1.e-3*zetal*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius)))
}

FUNCTION betl(v(mV)) {
    betl = exp(1.e-3*zetal*gml*(v-vhalfl-sh)*9.648e4/(8.315*(273.16+celsius)))
}

DERIVATIVE states {     : exact when v held constant; integrates over dt step
    rates(v)
    n' = (ninf - n) / taun
    l' = (linf - l) / taul
}

PROCEDURE rates(v (mV)) { :callable from hoc
    LOCAL a,qt
    qt = q10^((celsius-24)/10)

    a = alpn(v)
    ninf = 1/(1 + a)
    taun = betn(v)/(qt*a0n*(1+a))
    if (taun<nmin) {
        taun=nmin
    }

    a = alpl(v)
    linf = 1/(1+ a)
    taul = 0.26*(v+50-sh)/qtl
    if (taul<lmin/qtl) {
        taul=lmin/qtl
    }
}