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 neuron; 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 neuron; 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 Fast transient sodium current

NEURON {
    THREADSAFE
    SUFFIX naf
    USEION na READ ena WRITE ina
    RANGE gbar, gna, ina, mVhalf, hVhalf, mSlope, hSlope, taum, tauh, taun, base, factor
    POINTER pka
}

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

PARAMETER {
    gbar = 0.0 (S/cm2) 
    q = 1.8
    mVhalf     = -25.0 (mV)
    hVhalf     = -62.0 (mV)
    mSlope     =  -9.2 (mV)
    hSlope     =   6.0 (mV)
    taum       =   0.09 (ms)
    taun       =   0.34 (ms)
    tauh       =   0.34 (ms)
    base   = 0.0      : set in simulation file (if used)  
	factor = 0.0      : set in simulation file (if used)
} 

ASSIGNED {
    v (mV)
    ena (mV)
    ina (mA/cm2)
    gna (S/cm2)
    minf
    mtau (ms)
    hinf
    htau (ms)
    pka (1)
}

STATE { m h }

BREAKPOINT {
    SOLVE states METHOD cnexp
    gna = modulation() * gbar*m*m*m*h
    ina = gna*(v-ena)
}

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

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

PROCEDURE rates() {
    UNITSOFF
    minf = 1 / (1 + exp( (v-mVhalf) / mSlope ) )
    hinf = 1 / (1 + exp( (v-hVhalf) / hSlope ) )
    
    mtau = 0.38 + 1/( 0.6*exp((v-(-58.0))/8.0) + 1.8*exp((v-(-58.0))/(-35.0))  )
    
    if (v < - 60) {
        htau = 3.4 + 0.015*v
    }else{
        htau = 0.56 + 1.1/(1+exp((v-(-48))/15.0)) + 1.2/(1+exp((v-(-48))/4.0))
    }
        
    :mtau = 0.13 +1/(0.6*exp((v-(-58))/taum)+1.8*exp((v-(-58))/(taun)))
    :htau = 0.14 +1.2/(1+exp((v-(-32))/tauh))
    UNITSON
}

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

COMMENT

TODO:
update kintetics of inactivation gate below -60 mV, from linear to sigmoidal?
--------------------------------------------------------------------------------------

Original data by Ogata (1990), guinea pig, 22 C.

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

NEURON implementation by Alexander Kozlov <akozlov@csc.kth.se>, smooth
fit of mtau and htau. 

Updates by Robert Lindroos
channel kinetics updated so that natural instead of base 10 logarithm is used for 
values in Ogata 1990. This also reduces the AHP and spike frequency.
The revision of Ogata 1990, was done following a scanning of m and h gate parameters
that reduced the AHP magnitude.

Q factor of 1.8 used. Based on 
"The effect of temperature on Na currents in rat myelinated nerve fibres"
-> Q10 between 40 and 20 C 1.8-2.1
lowest value chousen since spiking is still intact and this make the cell fire slightly slower

ENDCOMMENT

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