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

 Download zip file 
Help downloading and running models
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]
Citations  Citation Browser
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 HVA L-type calcium current (Cav1.2)

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

    SUFFIX cal12
    USEION cal READ cali, calo WRITE ical VALENCE 2
    RANGE pbar, ical, base, factor
    POINTER pka

    pbar = 0.0 (cm/s)
    a = 0.17
    :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)
    ical (mA/cm2)
    ecal (mV)
    celsius (degC)
    cali (mM)
    calo (mM)
    mtau (ms)
    htau (ms)
    pka (1)

STATE { m h }

    SOLVE states METHOD cnexp
    ical = modulation() * pbar*m*(h*a+1-a)*ghk(v, cali, calo)

    m = minf
    h = hinf

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

PROCEDURE rates() {
    minf = 1/(1+exp((v-(-8.9))/(-6.7)))
    :mtau = 0.06+1/(0.06*exp((v-(-46))/20)+0.41*exp((v-26)/-48))
    mtau = 0.06+1/(exp((v-10)/20)+exp((v-(-17))/-48))
    hinf = 1/(1+exp((v-(-13.4))/11.9))
    htau = 44.3

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)


Activation curve was reconstructed for cultured NAc neurons from P5-P32
Charles River rat pups [1].   Activation time constant is from the
rodent neuron culture (both rat and mouse cells), room temperature 22-25
C [2, Fig.15A]. Inactivation curve of CaL v1.3 current was taken from HEK
cells [3, Fig.2 and p.819] at room temperature.

Original NEURON model by Wolf (2005) [4] was modified by Alexander Kozlov
<>. Kinetics of m1h type was used [5,6]. Activation
time constant was refitted to avoid singularity.

[1] Churchill D, Macvicar BA (1998) Biophysical and pharmacological
characterization of voltage-dependent Ca2+ channels in neurons isolated
from rat nucleus accumbens. J Neurophysiol 79(2):635-47.

[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] Bell DC, Butcher AJ, Berrow NS, Page KM, Brust PF, Nesterova A,
Stauderman KA, Seabrook GR, Nurnberg B, Dolphin AC (2001) Biophysical
properties, pharmacology, and modulation of human, neuronal L-type
(alpha(1D), Ca(V)1.3) voltage-dependent calcium currents. J Neurophysiol

[4] 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.

[5] Evans RC, Morera-Herreras T, Cui Y, Du K, Sheehan T, Kotaleski JH,
Venance L, Blackwell KT (2012) The effects of NMDA subunit composition on
calcium influx and spike timing-dependent plasticity in striatal medium
spiny neurons. PLoS Comput Biol 8(4):e1002493.

[6] Tuckwell HC (2012) Quantitative aspects of L-type Ca2+ currents. Prog
Neurobiol 96(1):1-31.