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

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

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: 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]

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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):	Neostriatal cholinergic interneuron;
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;
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: Neostriatal cholinergic interneuron; D2; I Na,t; I K; I h; I K,Ca; I Sodium; I Calcium; I Potassium;

Model files

Help downloading and running models

NEURON mod files from the paper:

Nicolas Maurice, Jeff Mercer, C. Savio Chan, Salvador Hernandez-Lopez,
Joshua Held, Tatiana Tkatch, and D. James Surmeier D2 Dopamine
Receptor-Mediated Modulation of Voltage-Dependent Na+ Channels Reduces
Autonomous Activity in Striatal Cholinergic Interneurons, J
Neurosci. 2004 Nov 17;24(46):10289-301.

This is the model demonstrated in Figure 10.G:

Figure 10. Modest reduction of Na+ channel currents mimics D2 receptor
effects on pacemaking...G, In a simulation of pacemaking (Na+ channel
density of 1.4 mS/cm2), mimicking the D2 receptor modulation by
selectively increasing Na+ channel entry into a slow-inactivated state
(as in D, E) slowed the discharge rate by >40%. Restoration of the
control values for this rate constant restored the discharge rate.

Sample model usage:

To mimic the modulation of the D2 receptor, use the "Set Value 1" and
"Set Value 2" buttons in the Change Variable Value panel.  This should
show the decrease in discharge rate seen in Figure 10.G.

Questions on how to use this model can be directed to Josh Held,
j-held@northwestern.edu

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