Deciphering neuron-glia compartmentalization in cortical energy metabolism.

Energy demand is an important constraint on neural signaling. Several methods have been proposed to assess the energy budget of the brain based on a bottom-up approach in which the energy demand of individual biophysical processes are first estimated independently and then summed up to compute the brain's total energy budget. Here, we address this question using a novel approach that makes use of published datasets that reported average cerebral glucose and oxygen utilization in humans and rodents during different activation states. Our approach allows us (1) to decipher neuron-glia compartmentalization in energy metabolism and (2) to compute a precise state-dependent energy budget for the brain. Under the assumption that the fraction of energy used for signaling is proportional to the cycling of neurotransmitters, we find that in the activated state, most of the energy ( approximately 80%) is oxidatively produced and consumed by neurons to support neuron-to-neuron signaling. Glial cells, while only contributing for a small fraction to energy production ( approximately 6%), actually take up a significant fraction of glucose (50% or more) from the blood and provide neurons with glucose-derived energy substrates. Our results suggest that glycolysis occurs for a significant part in astrocytes whereas most of the oxygen is utilized in neurons. As a consequence, a transfer of glucose-derived metabolites from glial cells to neurons has to take place. Furthermore, we find that the amplitude of this transfer is correlated to (1) the activity level of the brain; the larger the activity, the more metabolites are shuttled from glia to neurons and (2) the oxidative activity in astrocytes; with higher glial pyruvate metabolism, less metabolites are shuttled from glia to neurons. While some of the details of a bottom-up biophysical approach have to be simplified, our method allows for a straightforward assessment of the brain's energy budget from macroscopic measurements with minimal underlying assumptions