Analysis of the effects of modulatory agents on a modeled bursting neuron: dynamic interactions between voltage and calcium dependent systems

Abstract. In a computational model of the bursting neuron R15, we have implemented proposed mechanisms for the modulation of two ionic currents (IR and IsI) that play key roles in regulating its spontaneous electrical activity. The model was sufficient o simulate awide range of endogenous activity in the presence of various concentrations of serotonin (5-HT) or dopamine (DA). The model was also sufficient o simulate the responses of the neuron to-extrinsic urrent pulses and the ways in which those responses were altered by 5-HT or DA. The results suggest that the actions of modulatory agents and second messengers on this neuron, and presumably other neurons, cannot be understood on the basis of their direct effects alone. It is also necessary to take into account he indirect effects of these agents on other unmodulated ion channels. These indirect effects occur through the dynamic interactions of voltage-dependent a d calcium-dependent processes