Effects of Dopamine Modulation and KIR Inactivation in NAc Medium Spiny Neurons (Steephen 2011)

Due to the involvement of nucleus accumbens (NAc) medium spiny neurons (MSNs) in diverse behaviors, their excitability changes can have broad functional significance. Dopamine modulates the biophysical behavior of MSNs. In ~40% of MSNs, inward rectifying potassium (KIR) currents inactivate significantly, imparting greater excitability. Employing a 189-compartment computational model of the MSN and using spatiotemporally distributed synaptic inputs, the regulation of excitability by KIR inactivation and dopaminergic modulation was investigated and quantitatively characterized. It was shown that by forming different combinations, these regulating agents could fine tune MSN excitability across a wide range. With existing evidence indicating MSNs with and without KIR inactivation to be the likely targets for D2- and D1-receptor mediated modulations, respectively, the present findings suggest that dopaminergic channel modulation may intensify the existing excitability difference between them by suppressing the excitability of MSNs without KIR inactivation while further enhancing the excitability of the more excitable MSNs with KIR inactivation. On the other hand, the combined modulation of channels and synapses by dopamine may reverse the relative excitability of one cell type with respect to the other. This model contains a complete biophysical model of MSN cell. The application allows the user to vary the cell properties by choosing the type of KIR channels included (inKIR or non-inKIR), the type of Dopamine receptors (D1R or D2R) and the modulation mechanism (Intrinsic modulation , Intrinsic-synaptic modulation, or No modulation). The user can also choose between the single pulse current clamp stimulation or a physiologically realistic synaptic stimulation scheme. More details are available in the Help provided with the application.

Model Type: Neuron or other electrically excitable cell

Region(s) or Organism(s): Striatum; Basal ganglia

Cell Type(s): Nucleus accumbens spiny projection neuron

Currents: I Potassium; Kir; I CAN; I Calcium; I Na,p; I Krp; I L high threshold; I T low threshold; I p,q; I A; I K,Ca; I A, slow; I R; Kir, inactivating

Receptors: NMDA; AMPA; Gaba

Genes: IRK

Transmitters: Dopamine

Model Concept(s): Action Potential Initiation; Action Potentials; Ion Channel Kinetics; Delay; Neuromodulation; Synaptic Integration

Simulation Environment: NEURON

Implementer(s): Steephen, John Eric [johneric at duk.ac.in]; Padmakumar, Mithun [mithun.padmakumar at duk.ac.in]


Steephen JE. (2011). Excitability range of medium spiny neurons widens through the combined effects of inward rectifying potassium current inactivation and dopaminergic modulation Neurocomputing. 74

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