Enhancement of calcium responses by K_IR current inactivation in medium spiny neurons

Synaptic plasticity within cortico-striatal circuits critically influences learning and behavior, with the nucleus accumbens (NAc) serving as a key mediating structure. Within the NAc, medium spiny neurons (MSNs) are known to mediate input integration, whose dendritic calcium levels are thought to influence cortico-striatal plasticity. Calcium responses have been observed to correlate with firing frequency and earlier firing onset. Inward rectifying potassium (K_IR) currents inactivate significantly in ~40% of NAc MSNs. Studies have shown that this inactivation enhances firing frequency and advances firing onset. On the basis of these findings, we hypothesized that K_IR inactivation may enhance intracellular calcium levels in MSNs, with implications for synaptic plasticity. Using an 189-compartment computational model of the MSN, the influence of K_IR inactivation on calcium dynamics was investigated. We found that the amplitude of calcium influx was more than twice as large in the tertiary dendrite and at least 9% higher for higher input currents in response to K_IR inactivation. Additionally, the average calcium concentration increased by up to 26.1% in the soma, with enhancements of 4.3-21.4% in the dendrites. Our findings suggest that K_IR inactivation may significantly modulate synaptic plasticity, thereby impacting the learning mediated by the NAc core.