Behavioral correlates of differences in neural metabolic capacity

Cytochrome oxidase is a rate-limiting enzyme in oxidative phosphorylation, the major energy-synthesizing pathway used by the central nervous system, and cytochrome oxidase histochemistry has been extensively utilized to map changes in neural metabolism following experimental manipulations. However, the value of cytochrome oxidase activity in predicting behavior has not been analyzed. We argue that this endeavor is important because genetic composition and embryonic environment can engender differences in baseline neural metabolism in pertinent neural circuits, and these differences could represent differences in the degree to which specific behaviors are 'primed.' Here we review our studies in which differences in cytochrome oxidase activity and in behavior were studied in parallel. Using mammalian and reptilian models, we find that embryonic experiences that shape the propensity to display social behaviors also affect cytochrome oxidase activity in limbic brain areas, and elevated cytochrome oxidase activity in preoptic, hypothalamic, and amygdaloid nuclei correlates with heightened aggressive and sexual tendencies. Selective breeding regimes were used to create rodent genetic lines that differ in their susceptibility to display learned helplessness and in behavioral excitability. Differences in cytochrome oxidase activity in areas like the paraventricular hypothalamus, frontal cortex, habenula, septum, and hippocampus correlate with differences in susceptibility to display learned helplessness, and differences in activity in the dentate gyrus and perirhinal and posterior parietal cortex correlate with differences in hyperactivity. Thus, genetic and embryonic manipulations that engender specific behavioral differences produce specific neurometabolic profiles. We propose that knowledge of neurometabolic differences can yield valuable predictions about behavioral phenotype in other systems.