Striatal D1R medium spiny neuron, including a subcellular DA cascade (Lindroos et al 2018)

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Accession:237653
We are investigating how dopaminergic modulation of single channels can be combined to make the D1R possitive MSN more excitable. We also connect multiple channels to substrates of a dopamine induced subcellular cascade to highlight that the classical pathway is too slow to explain DA induced kinetics in the subsecond range (Howe and Dombeck, 2016. doi: 10.1038/nature18942)
Reference:
1 . Lindroos R, Dorst MC, Du K, Filipovic M, Keller D, Ketzef M, Kozlov AK, Kumar A, Lindahl M, Nair AG, Pérez-Fernández J, Grillner S, Silberberg G, Hellgren Kotaleski J (2018) Basal Ganglia Neuromodulation Over Multiple Temporal and Structural Scales-Simulations of Direct Pathway MSNs Investigate the Fast Onset of Dopaminergic Effects and Predict the Role of Kv4.2. Front Neural Circuits 12:3 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Axon; Channel/Receptor; Dendrite; Molecular Network; Synapse; Neuron or other electrically excitable cell;
Brain Region(s)/Organism: Basal ganglia; Striatum;
Cell Type(s): Neostriatum medium spiny direct pathway GABA cell; Neostriatum spiny neuron;
Channel(s): I A; I A, slow; I Calcium; I CAN; I K; I K,Ca; I K,leak; I Krp; I Na,t; I Potassium; I R; I T low threshold; Kir;
Gap Junctions:
Receptor(s): D1; Dopaminergic Receptor; AMPA; Gaba; NMDA;
Gene(s):
Transmitter(s): Dopamine; Gaba; Glutamate;
Simulation Environment: NEURON; Python;
Model Concept(s): Action Potentials; Detailed Neuronal Models; Electrical-chemical; G-protein coupled; Membrane Properties; Neuromodulation; Multiscale; Synaptic noise;
Implementer(s): Lindroos, Robert [robert.lindroos at ki.se]; Du, Kai [kai.du at ki.se]; Keller, Daniel ; Kozlov, Alexander [akozlov at nada.kth.se];
Search NeuronDB for information about:  Neostriatum medium spiny direct pathway GABA cell; D1; AMPA; NMDA; Gaba; Dopaminergic Receptor; I Na,t; I T low threshold; I A; I K; I K,leak; I K,Ca; I CAN; I Calcium; I Potassium; I A, slow; I Krp; I R; Kir; Dopamine; Gaba; Glutamate;
TITLE R-type calcium current (Cav2.3)

UNITS {
    (mV) = (millivolt)
    (mA) = (milliamp)
    (S) = (siemens)
    (molar) = (1/liter)
    (mM) = (millimolar)
    FARADAY = (faraday) (coulomb)
    R = (k-mole) (joule/degC)
}

NEURON {
    SUFFIX car
    USEION ca READ cai, cao WRITE ica VALENCE 2
    RANGE pbar, ica
}

PARAMETER {
    pbar = 0.0 (cm/s)
    :q = 1	: room temperature 22 C
    q = 3	: body temperature 35 C
} 

ASSIGNED { 
    v (mV)
    ica (mA/cm2)
    eca (mV)
    celsius (degC)
    cai (mM)
    cao (mM)
    minf
    mtau (ms)
    hinf
    htau (ms)
}

STATE { m h }

BREAKPOINT {
    SOLVE states METHOD cnexp
    ica = pbar*m*m*m*h*ghk(v, cai, cao)
}

INITIAL {
    rates()
    m = minf
    h = hinf
}

DERIVATIVE states { 
    rates()
    m' = (minf-m)/mtau*q
    h' = (hinf-h)/htau*q
}

PROCEDURE rates() {
    UNITSOFF
    minf = 1/(1+exp((v-(-29))/(-9.6)))
    mtau = 5.1*3
    hinf = 1/(1+exp((v-(-33.3))/17))
    htau = 22+80/(1+exp((v-(-19))/5))
    UNITSON
}

FUNCTION ghk(v (mV), ci (mM), co (mM)) (.001 coul/cm3) {
    LOCAL z, eci, eco
    z = (1e-3)*2*FARADAY*v/(R*(celsius+273.15))
    if(z == 0) {
        z = z+1e-6
    }
    eco = co*(z)/(exp(z)-1)
    eci = ci*(-z)/(exp(-z)-1)
    ghk = (1e-3)*2*FARADAY*(eci-eco)
}

COMMENT

Original data by Foehring  et al (2000) [1] for dissociated MSNs from
P28-P42 Sprague-Dawley rat brain. Unspecified recording temperature. The
liquid junction potential was around 8 mV and was not corrected. Kinetics
of m3h type was fitted.  Inactivation time constants were measured in
neurons from endopiriform nucleus of P7-P21 Hartley guinea pigs [2]
at room temperature 22 C.

Original NEURON model by Wolf (2005) [3] modified by Alexander Kozlov
<akozlov@kth.se>. Activation curve fitted to m3 kinetics [4],
activation time constant scaled up as well. Smooth fit of inactivation
time constant from [2,3].

[1] Foehring RC, Mermelstein PG, Song WJ, Ulrich S, Surmeier DJ
(2000) Unique properties of R-type calcium currents in neocortical and
neostriatal neurons. J Neurophysiol 84(5):2225-36.

[2] Brevi S, de Curtis M, Magistretti J (2001) Pharmacological and
biophysical characterization of voltage-gated calcium currents in the
endopiriform nucleus of the guinea pig. J Neurophysiol 85(5):2076-87.

[3] Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M,
O'Donnell P, Finkel LH (2005) NMDA/AMPA ratio impacts state transitions
and entrainment to oscillations in a computational model of the nucleus
accumbens medium spiny projection neuron. J Neurosci 25(40):9080-95.

[4] Evans RC, Maniar YM, Blackwell KT (2013) Dynamic modulation of
spike timing-dependent calcium influx during corticostriatal upstates. J
Neurophysiol 110(7):1631-45.

ENDCOMMENT

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