The brain receives most of its energy from oxidative metabolism, of which cytochrome oxidase is a key energy-deriving enzyme. There is tight coupling between neuronal activity and energy expenditure. Likewise, our previous studies have revealed the close correlation between the level of cytochrome oxidase and that of neuronal activity. The major goal of our proposed research is to understand the cellular basis of the dynamic metabolic adjustment of neurons to altered functional demand in the adult. That is, we wish to know if there are metabolically distinct classes of neurons within a single nuclear group, and whether they respond differently to varying levels of functional insult. The dorsal lateral geniculate nucleus of adult cat is chosen for this study, because it has well-defined physiological and morphological cell types and because experimental manipulations can be applied to the retina without physically invading the LGN itself. To begin with, we will analyze and quantify the metabolic characteristics of large, medium and small cells in the LGN at both the light and E.M. levels by means of cytochrome oxidase histo- and cyto-chemistry. We will attempt to correlate these metabolic indentities with the known sizes, distribution and physiological properties of X-, Y- and W-cells. We then wish to ask whether and how these cell types respond differently to varying degrees of trauma: (a) Sensory deprivation by means of monocular lid suture, which reduces but not eliminate the amount of natural stimulus (light) from entering the eye; (b) afferent impulse blockade by means of intravitreal injection of tetrodotoxin, at dosage that does not block axoplasmic transport; and (c) deafferentation my means of unilateral enucleation, which effectively eliminates both afferent impulses as well as presumed """"""""trophic"""""""" factors. We wish to know if these procedures would bring about varying degrees of responses in the LGN neurons, whether all neurons respond similarly to each type of trauma, or whether a specific cell type suffer a greater or lesser degree of susceptibility. These differences will be quantified at the light and E.M. levels. We hope that these data will help us gain a better understanding of the dynamic aspect of cellular response to functional deprivation in the adult nervous system.
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