Sodium dynamics underlying burst firing and putative mechanisms for the regulation of the firing pattern in midbrain dopamine neurons: A computational approach

A physiologically based multicompartmental computational model of a midbrai n dopamine (DA) neuron, calibrated using data from the literature, was deve loped and used to test the hypothesis that sodium dynamics drive the genera tion of a slow oscillation postulated to underlie NMDA-evoked bursting acti vity in a slice preparation. The full compartmental model was reduced to th ree compartments and ultimately to two variables, while retaining the bioph ysical interpretation of all parameters. A phase-plane analysis then sugges ted two mechanisms for the regulation of the firing pattern: (1) bursting a ctivity is favored by manipulations that enhance the region of negative slo pe in the whole-cell IV curve and inhibited by those manipulations, such as increasing linear currents, that tend to dampen this region and (2) assumi ng a region of negative slope is present in the IV curve, the bias of the s ystem can be altered, either enabling or disabling bursting. The model prov ides a coherent framework for interpreting the effects of glutamate, aspart ate, NMDA, and GABA agonists and antagonists under current-clamp conditions , as well as the effects of NMDA and barium under voltage-clamp conditions.