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

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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)
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]
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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;
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]; Du, Kai [kai.du at]; Keller, Daniel ; Kozlov, Alexander [akozlov at];
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 N-type calcium current (Cav2.2)

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

    SUFFIX can
    USEION ca READ cai, cao WRITE ica VALENCE 2
    RANGE pbar, ica, base, factor
    POINTER pka

    pbar = 0.0 (cm/s)
    a = 0.21
    :q = 1	: room temperature 22-25 C
    q = 2	: body temperature 35 C
    base   = 0.0      : set in simulation file    
	factor = 0.0      : set in simulation file

    v (mV)
    ica (mA/cm2)
    eca (mV)
    celsius (degC)  
    cai (mM)
    cao (mM)
    mtau (ms)
    htau (ms)
    pka (1)

STATE { m h }

    SOLVE states METHOD cnexp
    ica = modulation() * pbar*m*m*(h*a+1-a)*ghk(v, cai, cao)

    m = minf
    h = hinf

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

PROCEDURE rates() {
    minf = 1/(1+exp((v-(-3))/(-8)))
    :mtau = (0.06+1/(0.033*exp((v-(-36))/18)+0.35*exp((v-15)/-44)))*2
    mtau = (0.06+1/(exp((v-25)/18)+exp((v-(-31))/-44)))*2
    hinf = 1/(1+exp((v-(-74.8))/6.5))
    htau = 70

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)

FUNCTION modulation() {
    : returns modulation factor
    modulation = 1 + factor * (pka - base)


Model is based on mixed data. Activation curve is from neostriatal
medium spinal neurons of adult P28+ rats [1, Fig.12F], unspecified
recording temperature. Potentials were not corrected for the liquid
junction potential, which was estimated to be 7 mV.  Activation time
constant is from the rodent neuron culture (both rat and mouse cells),
room temperature 22-25 C [2, Fig.15B].  Inactivation data is from human
(HEK) cells [3, Tab.1, Tab.2], supposedly at room temperature.

Kinetics of m2h type is used [2, Fig.5]. Activation of m2 type is
fitted to the experimental data [1,4], activation time constant [2]
is scaled up as well.  Original NEURON model [5,4] was modified by
Alexander Kozlov <>. Activation time constant was refitted
to avoid singularity in the expression.

[1] Bargas J, Howe A, Eberwine J, Cao Y, Surmeier DJ (1994) Cellular
and molecular characterization of Ca2+ currents in acutely isolated,
adult rat neostriatal neurons. J Neurosci 14(11 Pt 1):6667-86.

[2] Kasai H, Neher E (1992) Dihydropyridine-sensitive and
omega-conotoxin-sensitive calcium channels in a mammalian
neuroblastoma-glioma cell line. J Physiol 448:161-88.

[3] McNaughton NC, Randall AD (1997) Electrophysiological properties of
the human N-type Ca2+ channel: I. Channel gating in Ca2+, Ba2+ and Sr2+
containing solutions. Neuropharmacology 36(7):895-915.

[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.

[5] 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.