Simulation of Spontaneous Activity in Dopaminergic Neurons of Mouse Retina

Abstract

Abstract: : Purpose: To investigate roles of voltage-gated ion channels in the spontaneous activity of mouse dopaminergic amacrine (DA) cells using a computer simulation. Methods: The model consisted of a membrane capacitance in parallel with six currents: Na⁺ transient, Na⁺ persistent, K⁺ fast, K⁺ slow, K_A and Ca²⁺. Hodgkin-Huxley type equations to define the voltage and time-dependent activation and inactivation were implemented using Simulator for Neural Networks and Action Potentials (SNNAP) 7.1. Results: The model DA cell was spontaneously active with a wide range of starting membrane potentials and resembled mouse cells in many respects. The model cell reached +52 mV at the peak of the spikes and hyperpolarized to -59 mV between spikes; the threshold was -45 mV. The firing rate of the model DA cell was 6 Hz, and the duration of the spike was 4.3 msec at threshold. The rise time of the spike was 0.5 msec, and the decay time was 0.8 msec. The afterhyperpolarization of the model was more negative than observed experimentally, however. Na⁺ currents were essential for the spontaneous activity of the model DA cell. When either Na⁺ transient or Na⁺ persistent was completely blocked, the spontaneous activity of model DA cell was eliminated. With either Na⁺ current blocked, the model DA cell reached a steady resting voltage of approximately -50 mV, which was similar to the value of mouse DA cells after TTX application. When the K⁺ channels were partially blocked, the model DA cell fired broader spikes with lower amplitudes, which simulated the behavior of mouse DA cells in experiments using 4-AP. The K_A current played a larger role in regulating firing frequency than other K⁺ currents; when the amplitude of K_A was decreased, the firing rate increased dramatically. The Ca²⁺ current did not have much effect on the spontaneous activity. Conclusions: Like the mouse DA cell, the spontaneous activity of the model DA cell depended on Na⁺ currents. K⁺ currents influenced the shape and frequency of the spikes.

Keywords: computational modeling • ion channels • retina: proximal(bipolar, amacrine, and gangli