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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[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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DOI: https://doi.org/10.1007/s12038-011-9039-8