A METABOLIC MAP OF CYTOCHROME-OXIDASE IN THE RAT-BRAIN - HISTOCHEMICAL, DENSITOMETRIC AND BIOCHEMICAL-STUDIES

To examine brain patterns of metabolic and functional activity, the di stribution of cytochrome oxidase, a mitochondrial enzyme marker for ne uronal functional activity, was mapped throughout the rat brain. Mappi ng was done qualitatively by enzyme histochemistry of brain sections c ut in three planes (coronal, sagittal and horizontal), and quantitativ ely by optical densitometry of stained sections and by biochemical ass ays of brain tissue homogenates. Activity of the enzyme was distribute d in characteristic patterns and amounts that differed among various n eural pathways, brain nuclei, cerebral cortical areas and layers, and neuron types. Gray matter essentially always had higher enzyme activit y than did white matter, by a factor of eight- to 12-fold. Among diffe rent neural pathways, cytochrome oxidase activity was relatively high in special sensory, somatosensory and motor systems, and was relativel y low in associative, limbic, autonomic and visceral regulatory system s (though exceptional areas were present). Among 11 different neuron t ypes, nearly a two-ford range of histochemical staining intensities wa s observed, with the darkest staining in neurons of the mesencephalic trigeminal nucleus. The observed patterns of cytochrome oxidase activi ty were mostly similar to the patterns of 2-deoxyglucose uptake seen p reviously [Schwartz W. J. and Sharp F. R. (1978) J. comp. Neurol. 177, 335-360; Sokoloff L. et al. (1977) J. Neurochem. 28, 897-916] in cons cious, ''resting'' animals, though some differences were found. For ex ample, whereas 2-deoxyglucose uptake was about three-fold higher in gr ay matter than in white matter [Sokoloff L. et al. (1977) J. Neurochem . 28, 897-916], cytochrome oxidase activity was about eight- to 12-fol d higher. This and other discrepancies probably reflect basic technica l differences between these two methods. Compared to 2-deoxyglucose, c ytochrome oxidase is more specific for oxidative rather than glycolyti c metabolism, and more reflective of overall neuronal functional activ ity occurring over longer time periods lasting hours to weeks, rather than minutes. The anatomical resolution of cytochrome oxidase histoche mistry is also finer than that of 2-deoxyglucose autoradiography, exte nding to the electron microscopic level. The metabolic map of cytochro me oxidase activity reveals patterns of normal brain function, and may be useful as a baseline for comparison in studies of brain disease, d evelopment, ageing and plasticity.