The brain’s energy demands are remarkable both in their intensity and in their moment-to-moment dynamic range. This perspective considers the evidence for Warburg-like aerobic glycolysis during the transient metabolic response of the brain to acute activation, and it particularly addresses the cellular mechanisms that underlie this metabolic response.
The temporary uncoupling between glycolysis and oxidative phosphorylation led to the proposal of an astrocyte-to-neuron lactate shuttle whereby during stimulation, lactate produced by increased glycolysis in astrocytes is taken up by neurons as their primary energy source. However, direct evidence for this idea is lacking, and evidence rather supports that neurons have the capacity to increase their own glycolysis in response to stimulation; furthermore, neurons may export rather than import lactate in response to stimulation.
The possible cellular mechanisms for invoking metabolic resupply of energy in neurons are also discussed, in particular the roles of feedback signaling via adenosine diphosphate and feedforward signaling by calcium ions.
Our brains perform a wide variety of amazing computational feats, the major research attention of most neurobiologists. By comparison, brain metabolism has been dismissed by the term “housekeeping” and also by the blanket assertion of a principle of homeostasis: the notion that biological systems by their nature tend toward the (effortless) maintenance of constant internal conditions.
As biologists, we must question our assumptions: how constant are the internal conditions, and what are the mechanisms that help to maintain them? Understanding these homeostatic mechanisms and their limitations is critical to understanding the myriad ways in which our housekeeping systems can fail and produce the dysfunction associated with disease.
