ANALYSIS OF THE EFFECTS OF MODULATORY AGENTS ON A MODELED BURSTING NEURON - DYNAMIC INTERACTIONS BETWEEN VOLTAGE AND CALCIUM-DEPENDENT SYSTEMS

In a computational model of the bursting neuron R15, we have implement ed proposed mechanisms for the modulation of two ionic currents (I-R a nd I-SI) that play key roles in regulating its spontaneous electrical activity. The model was sufficient to simulate a wide range of endogen ous activity in the presence of various concentrations of serotonin (5 -HT) or dopamine (DA). The model was also sufficient to simulate the r esponses of the neuron to extrinsic current pulses and the ways in whi ch those responses were altered by 5-HT or DA. The results suggest tha t the actions of modulatory agents and second messengers on this neuro n, and presumably other neurons, cannot be understood on the basis of their direct effects alone. It is also necessary to take into account the indirect effects of these agents on other unmodulated ion channels . These indirect effects occur through the dynamic interactions of vol tage-dependent and calcium-dependent processes.