Dynamic changes in cytochrome oxidase activity in the amygdala following lesions of rewarding sites in the lateral hypothalamus.

The aim of this study was to evaluate neural changes in oxidative metabolism in amygdaloid sub-nuclei following unilateral electrolytic lesions of lateral hypothalamic sites that supported brain stimulation reward. A histochemical analysis of cytochrome oxidase activity, comparing lesioned to non-lesioned sides in the amygdala, revealed a significant reduction of oxidative metabolism in the cortical nucleus and, to a lesser degree, in the adjacent piriform cortex; this effect was observed 2-4 weeks after the lesion, with complete recovery by the eighth week in the case of the cortical nucleus only. No particular pattern in cytochrome oxidase activity was detected in other amygdaloid sub-nuclei that were examined, including the basolateral and medial nucleus. Within both structures, the most pronounced decreases in metabolic activity were observed at roughly the same level, corresponding to the posterolateral and posteromedial levels of the cortical nucleus and just anterior to the amygdalopiriform transition. These results suggest that within the amygdaloid complex, the cortical sub-nuclei and possibly the neighbouring piriform cortex contribute more to modulating lateral hypothalamic self-stimulation than components of the central extended amygdala.

A comparison of glycogen phosphorylase a and cytochrome oxidase histochemical staining in rat brain.

The utility of metabolic markers that index functional neuronal circuits is widely appreciated. The present study asks whether patterns of the metabolic enzyme, active glycogen phosphorylase, parallel those of the neuronal marker, cytochrome oxidase. Fresh frozen rat brain sections (30 microns) were processed for either active glycogen phosphorylase or cytochrome oxidase at each of ten levels of the neuraxis. Although these metabolic markers predominate in different cellular compartments--glycogen phosphorylase in the astrocytic compartment and cytochrome oxidase in the neuronal compartment--the patterns of high, moderate, and low levels of activity for both enzymes were generally parallel. These similarities extended to detailed patterns of heterogeneous staining within structures, in particular, to laminated and modular distribution within cerebral and cerebellar cortical structures. The modular distribution was evident in barrel structures in the cerebral cortex and in parasagittal compartments in the vermis of the cerebellum. Conspicuous differences between the two patterns occurred in white matter, in subcortical grey matter regions such as the nucleus accumbens, diagonal band, amygdala, and globus pallidus, and in the superior olivary nuclei of the brainstem as well as in nonneural structures such as the choroid plexus and ependyma. Discrete patchiness was characteristic of active glycogen phosphorylase distribution in the limbic neuropil of the dentate gyrus and entorhinal cortex. The strong parallels between active glycogen phosphorylase and cytochrome oxidase distribution support the view that glycogen phosphorylase, despite its glial localization, can reflect neuronal metabolic demands.

Self-stimulation: a rewarding decade.

In the past decade, there has been considerable emphasis on developing and refining the measurement instruments used to assess the rewarding effect of brain stimulation. These efforts have given rise to quantitative methods aimed at revealing the underlying neurophysiology and neuroanatomy by tracing the trajectories of the relevant neurons. In this paper, we summarize some of the quantitative findings that have resulted from research at the University of Ottawa in the neurobiology of motivated behavior. These include studies using markers to reveal which structures are metabolically activated by rewarding brain stimulation, comprehensive mapping of brain areas for self-stimulation and other stimulation-induced behaviors, and examination of the effects of benzodiazepines on feeding and reward.

Distribution of cytochrome oxidase in response to rewarding brain stimulation: effect of different pulse durations.

Cytochrome oxidase histochemistry was used to evaluate neuronal changes in oxidative metabolism in response to rewarding brain stimulation of the medial forebrain bundle. Rats with single lateral hypothalamic electrodes self-stimulated daily for ten days for trains of either 0.1 or 2.0 ms pulses that corresponded to about 75% of maximum responding. Quantitative comparison of stimulated-to-unstimulated sides revealed differences in relative optical density in few structures, notably in the lateral septal nucleus and the nucleus accumbens, when the brief pulse duration was used. In contrast, the longer pulse duration gave rise to metabolic increases in several dopaminergic projections, including the frontal cortex, olfactory tubercle, and lateral habenula, and also enhanced activity in the lateral septal nucleus. These data suggest that mesocorticolimbic structures may be implicated in medial forebrain bundle self-stimulation.