Ca+/HCN channel-dependent persistent activity in multiscale model of neocortex (Neymotin et al 2016)

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Accession:185858
"Neuronal persistent activity has been primarily assessed in terms of electrical mechanisms, without attention to the complex array of molecular events that also control cell excitability. We developed a multiscale neocortical model proceeding from the molecular to the network level to assess the contributions of calcium regulation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in providing additional and complementary support of continuing activation in the network. ..."
Reference:
1 . Neymotin SA, McDougal RA, Bulanova AS, Zeki M, Lakatos P, Terman D, Hines ML, Lytton WW (2016) Calcium regulation of HCN channels supports persistent activity in a multiscale model of neocortex Neuroscience 316:344-366 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Realistic Network; Neuron or other electrically excitable cell; Synapse; Channel/Receptor; Molecular Network;
Brain Region(s)/Organism: Neocortex;
Cell Type(s): Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic 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 2-3 interneuron; Neocortex layer 5 interneuron; Neocortex layer 6a interneuron;
Channel(s): I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; I_AHP; I_KD; Ca pump;
Gap Junctions:
Receptor(s): mGluR1; GabaA; GabaB; AMPA; NMDA; mGluR; Glutamate; Gaba; IP3;
Gene(s):
Transmitter(s): Gaba; Glutamate;
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Ion Channel Kinetics; Oscillations; Spatio-temporal Activity Patterns; Signaling pathways; Working memory; Attractor Neural Network; Calcium dynamics; Laminar Connectivity; G-protein coupled; Rebound firing; Brain Rhythms; Dendritic Bistability; Reaction-diffusion; Beta oscillations; Persistent activity; Multiscale;
Implementer(s): Neymotin, Sam [samn at neurosim.downstate.edu]; McDougal, Robert [robert.mcdougal at yale.edu];
Search NeuronDB for information about:  Neocortex V1 L6 pyramidal corticothalamic cell; Neocortex V1 L2/6 pyramidal intratelencephalic cell; Neocortex V1 interneuron basket PV cell; mGluR1; GabaA; GabaB; AMPA; NMDA; mGluR; Glutamate; Gaba; IP3; I Na,t; I L high threshold; I T low threshold; I A; I K; I M; I h; I K,Ca; I CAN; I Calcium; I_AHP; I_KD; Ca pump; Gaba; Glutamate;
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CaHDemo
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cagk.mod
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calts.mod *
can.mod *
cat.mod *
gabab.mod
IC.mod *
icalts.mod *
Ih.mod
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kap.mod
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MyExp2SynNMDABB.mod
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mpisim.py
netcfg.cfg
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screenshot.png
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simdat.py
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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)
: :::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::::


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
    }
}

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