Nucleus accumbens (NAc) is a major site of action for many drugs of abuse and is implicated in brain disorders like schizophrenia . NAc MS neurons possess an array of active channels (14 channels) that may influence their information processing . Experimental studies on the electrophysiological properties of the dendrites of MS neurons are very sparse due to their tiny structure. Here we use a computational model of the NAc MS neurons to investigate the role of KIR currents in the integration of excitatory synaptic inputs.
Using NEURON, a 189-compartment model of MS cell was built based on Wolf et al, 2005 . Co-localized NMDA-AMPA synapses were used to generate EPSPs.
50% reduction of dendritic KIR conductance (gKIR) augmented somatic and dendritic EPSP parameters such as amplitude, half-width, rise time and decay time (by 24%, 23%, 11%, and 53% respectively) (Figure 1A), indicating that the cell is driven towards temporal integration mode of action potential firing. Elevation of gKIR had converse effects, thereby driving the cell towards coincidence detection mode. Additionally, 50% reduction of gKIR enhanced EPSP amplitude normalization (from 43% in the native model to 52%) (Figure 1B) while it reduced normalization of EPSP temporal summation (summation increased from 31% in the native model to 60%, 50 Hz synaptic input) (Figure 1C), with the extent of normalization proportional to frequency of synaptic input. Our results indicated that cell excitability would increase with reduction in gKIR, subsequently observed as increase in spiking frequency on reducing gKIR (2 spikes in native model against 7 spikes for gKIR = 50% for the same current injected at the soma).
Figure 1. Reduction in gKIR results in increase of EPSP amplitude, half width, rise time and decay time (A), increase in amplitude normalization (B), and increase in temporal summation (C).
Thus, KIR currents significantly affect propagation and normalization of synaptic potentials in MS neurons. In view of the fact that dopamine powerfully modulates KIR conductance in MS neurons KIR channels may play an important role in setting the cell excitability in response to external modulatory influences.
Wolf JA, Moyer JT, Lazarewicz MT, Contreras D, Benoit-Marand M, O'Donnel P, Finkel LH: NMDA/AMPA ratio impacts state transitions and entrainment to oscillations in a computational model of the nucleus accumbens medium spiny projection neuron.