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

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.

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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

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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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Correspondence to Jessy John.

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[John J and Manchanda R 2011 Modulation of synaptic potentials and cell excitability by dendritic KIR and KAs channels in nucleus accumbens medium spiny neurons: A computational study. J. Biosci. 36 XXX–XXX] DOI10.1007/s12038-011-9039-8

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John, J., Manchanda, R. Modulation of synaptic potentials and cell excitability by dendritic KIR and KAs channels in nucleus accumbens medium spiny neurons: A computational study. J Biosci 36, 309–328 (2011). https://doi.org/10.1007/s12038-011-9039-8

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Keywords

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