Inactivation of K_IR current modulates subthreshold synaptic inputs in striatal medium spiny neurons: A computational study

Abstract

Nucleus accumbens (NAc) has been identified as a major structure of brain involved in goal-directed behavior and learning. However, the cellular mechanisms underlying this are still not clear. The medium spiny (MS) neurons, the primary neurons of NAc, possess a wide variety of dendritic active conductances that are capable of modulating the subthreshold synaptic inputs impinging on them. K_IR conductance, being a major conductance active during resting conditions, is a potential candidate to influence this modulation. In 40% of NAc MS neurons, the current through this conductance is found to inactivate significantly. In this study we investigate the role of this inactivation in modulating the subthreshold synaptic inputs and their integration. This in turn will influence the excitability of the cell as well as its synaptic plasticity that underlie the learning process in brain. We find that inactivation of K_IR current depolarizes the RMP of the cell and increases the cell’s input resistance. This enhanced input resistance, in turn, augments the EPSP parameters such as amplitude and half width, thus promoting better temporal summation of synaptic inputs and consequently will result in enhanced cell excitability.