Issues concerning the construction of a metabolic model for neuronal activation

The metabolic events underlying neuronal activity still remain the object of intense debate, in spite of the considerable amount of information provided from different experimental techniques. Indeed, several attempts at linking the cellular metabolic phenomena with the macroscopic physiological changes have not yet attained foolproof conclusions. The difficulties in drawing definitive conclusions are due primarily to the heterogeneity of the experimental procedures used in different laboratories, and also given the impossibility of extrapolating the findings obtained under stationary conditions (prolonged stimulation) to dynamic and transient phenomena. Recently, lactate has received much attention, following its proposal by Pellerin and Magistretti (1994; Proc. Natl. Acad. Sci. USA 91:10625-10629), instead of glucose, as the main substrate for neurons during activity. Several challenging aspects suggest the return to a more conventional view of neuronal metabolism, in which neurons are able to metabolize ambient glucose directly as their major substrate, also during activation.