A reduced model of DA neuronal dynamics that displays quiescence, tonic firing and bursting

Midbrain dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and in a manner dependent upon their activities, diffusely release dopamine (DA) to their targets. Recent experimental studies have shown that DAergic neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Past computational models for DA cell activity relied upon somatodendritic mechanisms in order to generate DA neuronal bursting. However, recent experimental studies indicate that burst firing can be generated somatically with the dendrites silenced. These somatically induced bursts have characteristics consistent with normal bursting, suggesting that a single-compartmental model should be sufficient for generating the observed DA neuronal dynamics. In this work, we introduce such a model for DA neuronal dynamics and demonstrate that this model captures the qualitative behavior of DAergic neuronal dynamics: quiescence, tonic firing and bursting. In our conductance-based approach, the interplay between the L-type calcium and the calcium dependent SK potassium channel provides a scaffold for the underlying oscillation for the pacemaker-like firing patterns. The model includes terms which can selectively block the SK conductance, which would correspond to pharmacological manipulations using the drug apamin. Our modeling studies are in line with experimental evidence that a reduction of the SK conductance often induces DA neuronal bursting. Moreover, our model can reproduce findings that burst firing can be elicited via stimulus driven events, manifested by rises in the amount of NMDA. This model for DA cell activity could be further sculpted to include more detailed second messenger signaling processes in order to elucidate key differences between the two principal classes of midbrain DA neurons: those of the ventral tegmental area and the substantia nigra pars compacta.