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 L6 pyramidal corticothalamic 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 V1 L6 pyramidal corticothalamic 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 nax
: Na current for axon. No slow inact.
: M.Migliore Jul. 1997
: added sh to account for higher threshold M.Migliore, Apr.2002
: thread-safe 2010-05-31 Ben Suter
: 2010-11-07 Ben Suter reformatting, renaming thegna to g, setting sh = 0 (was 8 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
: :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::


NEURON {
    SUFFIX nax
    USEION na READ ena WRITE ina
    RANGE  gbar, sh
:   GLOBAL minf, hinf, mtau, htau,thinf, qinf, Rb, Rg, qg
}

PARAMETER {
    v                   (mV)
    celsius             (degC)
    ena                 (mV)        : must be explicitly def. in hoc

    sh      = 0         (mV)
    gbar    = 0.010     (mho/cm2)

    tha     = -30       (mV)        : v 1/2 for act
    qa      = 7.2       (mV)        : act slope (4.5)
    Ra      = 0.4       (/ms)       : open (v)
    Rb      = 0.124     (/ms)       : close (v)

    thi1    = -45       (mV)        : v 1/2 for inact
    thi2    = -45       (mV)        : v 1/2 for inact
    qd      = 1.5       (mV)        : inact tau slope
    qg      = 1.5       (mV)
    mmin    = 0.02
    hmin    = 0.5
    q10     = 2
    Rg      = 0.01      (/ms)       : inact recov (v)
    Rd      = 0.03      (/ms)       : inact (v)

    thinf   = -50       (mV)        : inact inf slope
    qinf    = 4         (mV)        : inact inf slope
}


UNITS {
    (mA) = (milliamp)
    (mV) = (millivolt)
    (pS) = (picosiemens)
    (um) = (micron)
}

ASSIGNED {
    ina         (mA/cm2)
    g           (mho/cm2)
    minf
    hinf
    mtau        (ms)
    htau        (ms)
}

STATE { m h}

BREAKPOINT {
    SOLVE states METHOD cnexp
    g = gbar*m*m*m*h
    ina = g * (v - ena)
}

INITIAL {
    trates(v,sh)
    m = minf
    h = hinf
}

DERIVATIVE states {
    trates(v,sh)
    m' = (minf-m)/mtau
    h' = (hinf-h)/htau
}

PROCEDURE trates(vm,sh2) {
    LOCAL  a, b, qt
    qt = q10^((celsius-24)/10)

    a = trap0(vm,tha+sh2,Ra,qa)
    b = trap0(-vm,-tha-sh2,Rb,qa)
    mtau = 1/(a+b)/qt
    if (mtau<mmin) {
        mtau = mmin
    }
    minf = a/(a+b)

    a = trap0(vm,thi1+sh2,Rd,qd)
    b = trap0(-vm,-thi2-sh2,Rg,qg)
    htau =  1/(a+b)/qt
    if (htau<hmin) {
        htau = hmin
    }
    hinf = 1/(1+exp((vm-thinf-sh2)/qinf))
}

FUNCTION trap0(v,th,a,q) {
    if (fabs(v-th) > 1e-6) {
        trap0 = a * (v - th) / (1 - exp(-(v - th)/q))
    } else {
        trap0 = a * q
    }
}

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