Spontaneous activity of dopaminergic retinal neurons

Dopaminergic local circuit neurons in the retina (DA cells) show robust, spontaneous, tetrodotoxin-sensitive pacemaking. To investigate the mechanism underlying this behavior, we characterized the sodium current and a subset of the potassium currents in the cells in voltage-clamp experiments. We found that there is a persistent component of the sodium current in DA cells which activates at more depolarized potentials than the transient component of the current. The transient component was completely inactivated at -50 mV, but DA cells remained able to fire spontaneous action potentials when potassium channels were partially blocked and the membrane potential remained above -40 mV. Based on these electrophysiological data, we developed a reduced computer model that reproduced the major features of DA cells. In simulations at the physiological resting potential, the persistent component of the sodium current was both necessary and sufficient to account for spontaneous activity, and the major contribution of the transient component of the sodium current was to initiate the depolarization of the model cell during the interspike interval. When tonic inhibition was simulated by lowering the input impedance of the model cell, the transient component played a larger role.