Norepinephrine stimulates glycogenolysis in astrocytes to fuel neurons with lactate

Although efficient compared to computers, the human brain utilizes energy at 10-fold the rate of other organs by mass. How the brain is supplied with sufficient on-demand energy to support its activity in the absence of neuronal storage capacity remains unknown. Neurons are not capable of meeting their own energy requirements, instead energy supply in the brain is managed by an oligocellular cartel composed of neurons, glia and the local vasculature (NGV), wherein glia can provide the ergogenic metabolite lactate to the neuron in a process called the astrocyte-to-neuron shuttle (ANLS). The only means of energy storage in the brain is glycogen, a polymerized form of glucose that is localized largely to astrocytes, but its exact role and conditions of use are not clear. In this computational model we show that neuromodulatory stimulation by norepinephrine induces astrocytes to recover glucosyl subunits from glycogen for use in a glycolytic process that favors the production of lactate. The ATP and NADH produced support metabolism in the astrocyte while the lactate is exported to feed the neuron. Thus, rapid energy demands by both neurons and glia in a stimulated brain can be met by glycogen mobilization.