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 Slow A-type potassium current (Kv1.2)

NEURON {
    THREADSAFE
    SUFFIX kas
    USEION k READ ek WRITE ik
    RANGE gbar, gk, ik, base, factor
    POINTER pka
}

UNITS {
    (S) = (siemens)
    (mV) = (millivolt)
    (mA) = (milliamp)
}

PARAMETER {
    gbar = 0.0 (S/cm2) 
    q = 3
    a = 0.2
    base   = 0.0      : set in simulation file    
	factor = 0.0      : set in simulation file
} 

ASSIGNED {
    v (mV)
    ek (mV)
    ik (mA/cm2)
    gk (S/cm2)
    minf
    mtau (ms)
    hinf
    htau (ms)
    pka (1)
}

STATE { m h }

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

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

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

PROCEDURE rates() {
    LOCAL alpha, beta, sum
    UNITSOFF
    alpha = 0.25/(1+exp((v-50)/(-20)))
    beta = 0.05/(1+exp((v-(-90))/35))
    sum = alpha+beta
    minf = alpha/sum
    mtau = 1/sum

    alpha = 0.0025/(1+exp((v-(-95))/16))
    beta = 0.002/(1+exp((v-50)/(-70)))
    sum = alpha+beta
    hinf = a+(alpha/sum)*(1-a)
    htau = 1/sum
    UNITSON
}

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

COMMENT

Original data by Shen (2004), diss MSN, rat, room temp.

Genesis implementation by Kai Du <kai.du@ki.se>, MScell v9.5.

NEURON implementation by Alexander Kozlov <akozlov@csc.kth.se>.

ENDCOMMENT

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