Sites and Mechanisms of Function-Related Changes in Energy Metabolism in the Nervous System

Traditional neuroanatomical and electrophysiological methods to localize functional activities in the nervous system focus on perikarya as the sites of activity. Metabolic mapping of local functional activity in the nervous system with the deoxyglucose method has directed interest toward the activity in neuropil. Studies of local glucose utilization (lCMRglc) indicate that energy metabolism is increased by functional activation mainly in terminal projection zones of activated pathways. Electrical stimulation of a pathway raises lCMRglc in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, stimulation of the sciatic nerve produces frequency-dependent metabolic activation in the dorsal horn of the lumbar cord, where the axonal terminals of the afferent pathway reside, with no apparent metabolic effects in the cell bodies of the pathway in the dorsal root ganglia. Functional activation of the hypothalamo-hypophysial pathway by salt-loading increases lCMRglc in the neurohypophysis, the site of the terminal axons of the pathway, but not in the paraventricular and supraoptic nuclei, where the cell bodies of origin of the pathway reside. Activation by hypotension of pathways to these nuclei from brain stem structures involved in baroceptor reflexes does, however, increase lCMRglc in these nuclei. Depolarization induced by electrical stimulation, increased extracellular K+, or opening of Na+ channels with veratridine stimulate lCMRglc in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+,K(+)-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to trigger the function-related increase in energy metabolism. The metabolic activation is the consequence not of the functional activity itself but of processes operating to recover from that activity.