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 K-D channel with activation for motor cortex
: K-D current with activation, for motor cortex pyramidal neurons, per Miller et al. (2008)
: Based on K-A current K-A current for Mitral Cells from Wang et al (1996), by M.Migliore Jan. 2002
: 2011-02-25 Ben Suter, first version, using MM's kamt.mod as a starting template
: 2011-09-18 Ben Suter, set default parameter values to those found from MRF optimization for BS0284 model
:
: :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::
: Copyright 2011, Benjamin Suter
: 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 {
    THREADSAFE
    SUFFIX kdmc
    USEION k READ ek WRITE ik
    RANGE  gbar, minf, mtau, hinf, htau
    GLOBAL taumin
}

PARAMETER {
    gbar    = 0.002     (mho/cm2)

    celsius
    ek                  (mV)   : must be explicitly def. in hoc
    v                   (mV)

    : activation
    vhalfmt = -25       : original -20   : rough estimate from Miller et al (2008) Fig. 3D I-V curve
    km      = 14        : manual fit to match this I-V curve

    : inactivation
    : NOTE: These values are still quite arbitrary (but get about the correct htau at -40 and -30 mV
    vhalfh  = -5        : original -55
    zetah   = 0.02      : original 0.05
    gmh     = 0.2       : original 0.7
    a0h     = 0.00058   : original 0.00055
    taumin	= 0.1	(ms)		: minimal value of time constant

    vhalfht = -100      : original -88   : measured by Storm (1988)
    kh      = 8         : manual fit to match inactivation curve in Storm (1988) and Johnston+Wu textbook

    q10     = 3
}


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

ASSIGNED {
    ik      (mA/cm2)
    minf        mtau (ms)
    hinf        htau (ms)
}


STATE { m h }

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

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

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

PROCEDURE trates(v) {
    LOCAL qt
    qt   = q10^((celsius-34)/10)

    minf = 1/(1 + exp(-(v-vhalfmt)/km))
    mtau = 1

    hinf = 1/(1 + exp((v-vhalfht)/kh))
    htau = exp(zetah*gmh*(v-vhalfh)) / (qt*a0h*(1 + exp(zetah*(v-vhalfh))))
    if(htau < taumin) { htau = taumin } 	: min value of time constant
}

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