Conductance-Based Model of the Voltage-Dependent Generation of a Plateau Potential in Subthalamic Neurons

Abstract

Because the subthalamic nucleus (STN) acts as a driving force of the basal ganglia, it is important to know how the activities of STN neurons are regulated. Previously, we have reported that a subset of STN neurons generates a plateau potential in a voltage-dependent manner. These plateau potentials can be evoked only when the cell is hyperpolarized. Here, to examine the mechanism of the voltage-dependent generation of the plateau potential in STN neurons, we constructed a conductance-based model of the plateau-generating STN neuron based on experimental observations and compared simulation results with recordings in slices. The model consists of a single compartment containing a Na+ current, a delayed-rectifier K+ current, an A-type K+ current, an L-like long-lasting Ca2+ current, a T-type Ca2+ current, a Ca2+-dependent K+ current, and a leak current. Our simulation results showed that a plateau potential in the model could be induced in a voltage-dependent manner that depended on the inactivation properties of L-like long-lasting Ca2+ current. The model could also reproduce the generation of a plateau potential as a rebound potential after termination of hyperpolarizing current injection. In addition, we tested the stability of simulated plateau potentials against inhibitory perturbation and found that the model showed similar properties observed for the plateau potentials of STN neurons in slices. The effects of K+ channel blockade by TEA and intracellular Ca2+ ion chelation by BAPTA on the plateau duration were also tested in the model and were found to match experimental observations. Thus our STN neuron model could qualitatively reproduce a number of experimental observations on plateau potentials. Our results suggest that the inactivation of L-type Ca2+ channels plays an important role in the voltage-dependent generation of the plateau potential.