This work seeks first to understand the mechanisms responsible for the conversion of the regular, spontaneous firing that characterizes dopamine neurons in vitro into burst firing or irregular firing, and then to generalize to the situation in vivo as well as to the functioning of dopamine neurons within neural circuits. Previous work resulted in a comprehensive model of a dopamine neuron including calcium dynamics in the soma and sodium dynamics in flu: dendrites that account for a wide array of spontaneous and pharmacologically-induced oscillation in dopamine neurons in vitro as well as certain manipulations in vivo. Furthermore the model can be used to make predictions of dopaminergic activity in response to pharmaceutical agents. This model incorporates stochastic background levels of synaptic activation as well as by transient increases in this level such as one might expect when a reward is delivered or when a reward predicting stimulus is presented. A simplified circuit model of the role of dopamine neurons in reward mediated learning has been developed and will be fine tuned by abstracting essential features from the detailed dopamine neuron as well as from a biophysically detailed model of a striatal neuron. W; intend to develop a better understanding of dopaminergic signaling by vertical integration between the levels of modeling, with the goal ol gaining insights into diseases in which dopaminergic signaling is compromised.
Showing the most recent 10 out of 11 publications
