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Journal of Biosciences

, Volume 36, Issue 2, pp 309–328 | Cite as

Modulation of synaptic potentials and cell excitability by dendritic KIR and KAs channels in nucleus accumbens medium spiny neurons: A computational study

  • Jessy John
  • Rohit Manchanda
Article

Abstract

The nucleus accumbens (NAc), a critical structure of the brain reward circuit, is implicated in normal goal-directed behaviour and learning as well as pathological conditions like schizophrenia and addiction. Its major cellular substrates, the medium spiny (MS) neurons, possess a wide variety of dendritic active conductances that may modulate the excitatory post synaptic potentials (EPSPs) and cell excitability. We examine this issue using a biophysically detailed 189-compartment stylized model of the NAc MS neuron, incorporating all the known active conductances. We find that, of all the active channels, inward rectifying K+ (KIR) channels play the primary role in modulating the resting membrane potential (RMP) and EPSPs in the down-state of the neuron. Reduction in the conductance of KIR channels evokes facilitatory effects on EPSPs accompanied by rises in local input resistance and membrane time constant. At depolarized membrane potentials closer to up-state levels, the slowly inactivating A-type potassium channel (KAs) conductance also plays a strong role in determining synaptic potential parameters and cell excitability. We discuss the implications of our results for the regulation of accumbal MS neuron biophysics and synaptic integration by intrinsic factors and extrinsic agents such as dopamine.

Keywords

Computational model excitatory post synaptic potential (EPSP) inward rectifying K+ (KIR) channel medium spiny neurons nucleus accumbens slowly inactivating A-type potassium channel (KAsspiking 

Abbreviations

AMPA

alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

DA

dopamine

D1R

D1 receptor

D2R

D2 receptor

EPSPs

excitatory post synaptic potentials

GABA

gamma amino butyric acid

ISI

interspike interval

KIR

inward rectifying potassium

MS

medium spiny

NAc

nucleus accumbens

NMDA

N-methyl-d-aspartate

RMP

resting membrane potential

KAs

slowly inactivating A-type potassium

Notes

Acknowledgements

The authors would like to thank the Department of Biotechnology, New Delhi, for their financial support for this work (project no. BT/PR9599/Med/30/34/2007).

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Copyright information

© Indian Academy of Sciences 2011

Authors and Affiliations

  1. 1.Biomedical Engineering group, Department of Biosciences and BioengineeringIndian Institute of Technology BombayPowaiIndia

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