Mathematical modeling of the biphasic dopaminergic response to glucose

Abstract

In this work, we specify potential elements of the brain to sense and regulate the energy metabolism of the organism. Our numerical investigations base on neurochemical experiments demonstrating a biphasic association between brain glucose level and neuronal activity. The dynamics of high and low affine KATP channels are most likely to play a decisive role in neuronal activity. We develop a coupled Hodgkin-Huxley model describing the interactive behavior of inhibitory GABAergic and excitatory dopaminergic neurons projecting into the caudate nucleus. The novelty in our approach is that we include the synaptic coupling of GABAergic and dopaminergic neurons as well as the interaction of high and low affine KATP channels. Both are crucial mechanisms described by kinetic models. Simulations demonstrate that our new model is coherent with neurochemical in vitro experiments. Even experimental interventions with glibenclamide and glucosamine are reproduced by our new model. Our results show that the considered dynamics of high and low affine KATP channels may be a driving force in energy sensing and global regulation of the energy metabolism, which supports central aspects of the new Selfish Brain Theory. Moreover, our simulations suggest that firing frequencies and patterns of GABAergic and dopaminergic neurons are correlated to their neurochemical outflow.