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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS018122-07
Application #
3398202
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1981-07-01
Project End
1989-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Palmer, J M; Wong-Riley, M; Sharkey, K A (1998) Functional alterations in jejunal myenteric neurons during inflammation in nematode-infected guinea pigs. Am J Physiol 275:G922-35
Wong-Riley, M T; Mullen, M A; Huang, Z et al. (1997) Brain cytochrome oxidase subunit complementary DNAs: isolation, subcloning, sequencing, light and electron microscopic in situ hybridization of transcripts, and regulation by neuronal activity. Neuroscience 76:1035-55
Wong-Riley, M; Antuono, P; Ho, K C et al. (1997) Cytochrome oxidase in Alzheimer's disease: biochemical, histochemical, and immunohistochemical analyses of the visual and other systems. Vision Res 37:3593-608
Nie, F; Wong-Riley, M T (1996) Differential glutamatergic innervation in cytochrome oxidase-rich and -poor regions of the macaque striate cortex: quantitative EM analysis of neurons and neuropil. J Comp Neurol 369:571-90
Nie, F; Wong-Riley, M T (1996) Mitochondrial- and nuclear-encoded subunits of cytochrome oxidase in neurons: differences in compartmental distribution, correlation with enzyme activity, and regulation by neuronal activity. J Comp Neurol 373:139-55
Zhang, C; Wong-Riley, M T (1996) Do nitric oxide synthase, NMDA receptor subunit R1 and cytochrome oxidase co-localize in the rat central nervous system? Brain Res 729:205-15
LaManna, J C; Kutina-Nelson, K L; Hritz, M A et al. (1996) Decreased rat brain cytochrome oxidase activity after prolonged hypoxia. Brain Res 720:1-6
Zhang, C; Granstrom, L; Wong-Riley, M T (1996) Deafferentation leads to a down-regulation of nitric oxide synthase in the rat visual system. Neurosci Lett 211:61-4
Nie, F; Wong-Riley, M T (1996) Metabolic and neurochemical plasticity of gamma-aminobutyric acid-immunoreactive neurons in the adult macaque striate cortex following monocular impulse blockade: quantitative electron microscopic analysis. J Comp Neurol 370:350-66
Nie, F; Wong-Riley, M T (1995) Double labeling of GABA and cytochrome oxidase in the macaque visual cortex: quantitative EM analysis. J Comp Neurol 356:115-31

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