Regulation of substantia nigra dopamine neurons.

A substantial amount of research has focused on determining the factors that alter the activity of substantia nigra dopamine neurons. Much of this research has indicated that several mechanisms that regulate dopamine neuron activity have the capability to maintain the baseline activity of dopamine cells at a fairly constant rate. For example, the intrinsic membrane conductances present on dopamine neurons, which generate the spike activity of these cells, appear to maintain the activity of spontaneously active neurons and suppress the induction of activity in quiescent cells. In addition, dopamine cell activity can be regulated by afferent systems that appear to be capable of preventing dopamine neurons from displaying sustained variations in electrophysiological activity. Specifically, inputs from the striatum or from the subthalamic nucleus may each exert opposing influences on dopamine cell activity via direct vs. indirect afferent projection pathways. In addition, the dendritic release of dopamine may provide negative feedback; dopamine cell firing may increase the dendritic release of dopamine within the substantia nigra, providing a local feedback inhibition of dopamine neuron activity. Factors such as the intrinsic membrane properties, afferent input, and the dendritic release of dopamine all work together in a complex manner to regulate the activity level of dopamine neurons.