What makes DA neurons tick? Role of Ca2+ sources and inward currents in setting the regular pacemaking of dopaminergic neurons

Abstract

Dopamine (DA) neurons show regular, pacemaking fir-ing in the range 1-8 Hz inin vitro preparations. Thecurrents involved in this pacemaking behavior are notfully understood. The slow oscillatory potential (SOP),evident after the application of TTX, is known todepend on the mutual interaction between L-type Ca2+and small conductance (SK) K+ currents. The SOPoscillates in a frequency range similar to the pacemakingfiring rate and it is assumed to be responsible for deter-mining this pacemaking frequency [1]. However, recentresults indicate that the SOP’sfrequencyisnotcorre-lated with spontaneous pacemaking frequency [2,3].Furthermore there is experimental evidence indicatingthat pacemaking does not require the influx of Ca2+through L-type Ca2+ channels [4,5]. Figure 1A illus-trates this last point from a modeling approach. Theblack trace corresponds to the spontaneous firing of themodel DA neuron and in blue the SOP. After simulatedblock of L-type current no activity is observed (green)but this is recovered (red) by injecting a virtual L-typecurrent into the soma (cf. [5]). Figure 1B on the otherhand illustrates the possible role of the fast Na+ currentin reestablishing pacemaking. Black and blue traces aresimilar to those in panel A; however pacemaking is rees-tablished by shifting the Na+ activation curve in ahyperpolarization direction (green). We explore the role