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

Journal of biosciences

Jessy John1¹  Rohit Manchanda¹ 

[1] Biomedical Engineering group, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India$$

关键词: 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;   

DOI  :  

来源: Indian Academy of Sciences

【 摘 要 】

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.

【 授权许可】

Unknown