Function-related Changes in Energy Metabolism in the Nervous System: Localization and Mechanisms

Abstract

Previous neuroanatomical and electrophysiological methods to localize functional activity in the nervous system focus on perikarya as the sites of the activity. Metabolic mapping of local functional activity in the nervous system provides a new dimension, the activity in the neuropil. Studies of local glucose utilization have shown that energy metabolism is increased by functional activation, but the effects are mainly in the terminal projection zones of the activated pathway. Electrical stimulation of a pathway raises glucose utilization in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, electrical 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, but 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 glucose utilization in the pituitary neural lobe, where the terminal axons of the pathway reside, but not in the paraventricular and supraoptic nuclei, the sites of the cell bodies of origin of the pathway. Reflex activation by hypotension of pathways to these nuclei from brain stem structures involved in baroreceptor reflexes, however, increases glucose utilization in these nuclei. Depolarization induced by electrical stimulation, extracellular K⁺, or opening of Na⁺ channels with veratridine, stimulates glucose utilization 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 functional activation of energy metabolism. The metabolic activation appears, therefore, to be associated not directly with the functional activity but rather with the recovery from the consequences of that activity.