D2 dopamine receptor modulation of interneuronal activity (Maurice et al. 2004)

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Accession:98005
"... Using a combination of electrophysiological, molecular, and computational approaches, the studies reported here show that D2 dopamine receptor modulation of Na+ currents underlying autonomous spiking contributes to a slowing of discharge rate, such as that seen in vivo. Four lines of evidence support this conclusion. ... Fourth, simulation of cholinergic interneuron pacemaking revealed that a modest increase in the entry of Na+ channels into the slow-inactivated state was sufficient to account for the slowing of pacemaker discharge. These studies establish a cellular mechanism linking dopamine and the reduction in striatal cholinergic interneuron activity seen in the initial stages of associative learning." See paper for more and details.
Reference:
1 . Maurice N, Mercer J, Chan CS, Hernandez-Lopez S, Held J, Tkatch T, Surmeier DJ (2004) D2 dopamine receptor-mediated modulation of voltage-dependent Na+ channels reduces autonomous activity in striatal cholinergic interneurons. J Neurosci 24:10289-301 [PubMed]
Model Information (Click on a link to find other models with that property)
Model Type: Neuron or other electrically excitable cell;
Brain Region(s)/Organism:
Cell Type(s): Neostriatum interneuron ACh cell;
Channel(s): I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;
Gap Junctions:
Receptor(s): D2;
Gene(s): D2 DRD2; HCN1; HCN2;
Transmitter(s):
Simulation Environment: NEURON;
Model Concept(s): Activity Patterns; Action Potentials; Parkinson's;
Implementer(s): Held, Joshua [j-held at northwestern.edu];
Search NeuronDB for information about:  Neostriatum interneuron ACh cell; D2; I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;
COMMENT

c1 - c2 - c3 - c4 - o
|    |    |    |    |
i1 - i2 - i3 - i4 - i5 - is

ENDCOMMENT




NEURON {
	SUFFIX kv4_ch
	USEION k READ ek WRITE ik
	RANGE g, ik, gbar
	GLOBAL alpha, beta
	GLOBAL ci, ic, oi, io, a, b, am, bm, vc, gamma, delta, vha, vhb
	GLOBAL i5is, isi5
	GLOBAL q10i, q10v
}

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

PARAMETER {
	gbar = 1	(S/cm2)
	gamma = 200	(1/ms)
	delta = 4	(1/ms)
	a = 3
	b = 40
	ic = 500	(/ms)
	oi = 1e-9	(/ms)
	io = .01	(/ms)
	ci = .2		(/ms)
	am = 1		(1/ms)
	bm = 7		(1/ms)
	vc = 10		(mV)
	vha = -75	(mV)
	vhb = -30	(mV)
	i5is = .001	(/ms)
	isi5 = .001	(/ms)
	q10i = 3
	q10v = 3
	celsius		(degC)
}

ASSIGNED {
	v	(mV)
	ek	(mV)
	g	(S/cm2)
	ik	(mA/cm2)
	alpha	(/ms)
	beta	(/ms)
}

STATE {
	c1
	c2
	c3
	c4
	o
	i1
	i2
	i3
	i4
	i5
	is
}

BREAKPOINT {
	SOLVE kin METHOD sparse
	g = gbar*o
	ik = g*(v-ek)
}

INITIAL {
	SOLVE kin STEADYSTATE sparse
}

KINETIC kin{LOCAL q10
	q10 = q10i^((celsius - 22 (degC))/10 (degC))
	rates(v)
	~ c1 <-> c2 (3*alpha,beta)
	~ c2 <-> c3 (2*alpha,2*beta)
	~ c3 <-> c4 (alpha,3*beta)
	~ c4 <-> o  (q10*gamma,q10*delta)

	~ i1 <-> i2 (3*alpha*a,beta/b)
	~ i2 <-> i3 (2*alpha*a,2*beta/b)
	~ i3 <-> i4 (alpha*a,3*beta/b)
	~ i4 <-> i5 (q10*gamma,q10*delta)
	~ i5 <-> is (q10*i5is,q10*isi5)

	~ i1 <-> c1 (q10*ic,q10*ci)
	~ i2 <-> c2 (q10*ic/b,q10*ci*a)
	~ i3 <-> c3 (q10*ic/b^2,q10*ci*a^2)
	~ i4 <-> c4 (q10*ic/b^3,q10*ci*a^3)
	~ i5 <-> o  (q10*io,q10*oi)

	CONSERVE c1+c2+c3+c4+i1+i2+i3+i4+i5+o+is=1
}

PROCEDURE rates(v(millivolt)) {LOCAL q10
	q10 = q10v^((celsius - 22 (degC))/10 (degC))
	alpha = q10*am*exp((v-vha)/vc)
	beta = q10*bm*exp((v-vhb)/-vc)
}

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