Frequency switching in a two-compartmental model of the dopaminergic neuron.

Mid-brain dopaminergic (DA) neurons display two functionally distinct modes of electrical activity: low- and high-frequency firing. The high-frequency firing is linked to important behavioral events in vivo. However, it cannot be elicited by standard manipulations in vitro. We had suggested a two-compartmental model of the DA cell that united data on firing frequencies under different experimental conditions. We now analyze dynamics of this model. The analysis was possible due to introduction of timescale separation among variables. We formulate the requirements for low and high frequencies. We found that the modulation of the SK current gating controls the frequency rise under applied depolarization. This provides a new mechanism that limits the frequency in the control conditions and allows high-frequency responses to depolarization if the SK current gating is downregulated. The mechanism is based on changing Ca(2+) balance and can also be achieved by direct modulation of the balance. Interestingly, such changes do not affect the high-frequency oscillations under NMDA. Therefore, altering Ca(2+) balance allows combining the high-frequency response to NMDA activation with the inability of other treatments to effectively elevate the frequency. We conclude that manipulations affecting Ca(2+) balance are most effective in controlling the frequency range. This modeling prediction gives a clue to the mechanism of the high-frequency firing in the DA neuron in vivo and in vitro.