The primate visual cortex possesses a unique array of metabolically active zones that are rich in cytochrome oxidase activity. In area 17, these C.O.-rich supragranular puffs and the granular fourth layer appear to coincide in space with geniculocortical terminations, and are likely to be strongly influenced by subcortical sensory input. The major goal of our proposed research is to understand how the metabolic integrity of mature visual cortical neurons is governed by normal and altered retinal input. While there is a substantial amount of information on both the anatomical and functional adjustments in the developing visual system, little is known about such plasticity in the adult. In fact, the mature neuron has traditionally been regarded as refractory to the trauma of sensory deprivation. We propose to examine the effect of various forms of sensory insult on the level of cytochrome oxidase in the primate visual cortex. Since there is tight coupling between neuronal activity and energy metabolism, mainly via the oxidative pathway, the level of cytochrome oxidase, a key energy-deriving oxidative enzyme, can be used as an indicator of the level of neuronal activity. Three paradigms will be tested for differential cortical responsiveness: (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 injections of tetrodotoxin, at a dosage that does not block axoplasmic transport; and (c) deafferentation by means of unilateral enucleation, which effectively eliminates both afferent impulses as well as presumed """"""""trophic"""""""" factors. We wish to know if cortical neurons are seensitive to any or all of these treatments. Do all neurons respond uniformly to each type of trauma, or does a specific type of neuron suffer a grater or lesser degree of susceptibility? We also wish to know if the time course and degree of reaction differ between the puffs and lamina IV, between the magnorecipient IVC and the pavro-recipient IVC, and between the center and the periphery of cortical puffs. We hope that these data will help us gain a better understanding of the dynamic aspect of cellular response to functional deprivations in the adult visual system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005439-03
Application #
3260510
Study Section
Neurology A Study Section (NEUA)
Project Start
1984-07-01
Project End
1990-06-30
Budget Start
1986-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1986
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
Dhar, Shilpa S; Ongwijitwat, Sakkapol; Wong-Riley, Margaret T T (2008) Nuclear respiratory factor 1 regulates all ten nuclear-encoded subunits of cytochrome c oxidase in neurons. J Biol Chem 283:3120-9
Liang, H L; Ongwijitwat, S; Wong-Riley, M T T (2006) Bigenomic functional regulation of all 13 cytochrome c oxidase subunit transcripts in rat neurons in vitro and in vivo. Neuroscience 140:177-90
Liang, Huan Ling; Wong-Riley, Margaret T T (2006) Activity-dependent regulation of nuclear respiratory factor-1, nuclear respiratory factor-2, and peroxisome proliferator-activated receptor gamma coactivator-1 in neurons. Neuroreport 17:401-5
Yang, S J; Liang, H L; Wong-Riley, M T T (2006) Activity-dependent transcriptional regulation of nuclear respiratory factor-1 in cultured rat visual cortical neurons. Neuroscience 141:1181-92
Ongwijitwat, Sakkapol; Liang, Huan Ling; Graboyes, Evan M et al. (2006) Nuclear respiratory factor 2 senses changing cellular energy demands and its silencing down-regulates cytochrome oxidase and other target gene mRNAs. Gene 374:39-49
Wong-Riley, Margaret T T; Yang, Shou Jing; Liang, Huan Ling et al. (2005) Quantitative immuno-electron microscopic analysis of nuclear respiratory factor 2 alpha and beta subunits: Normal distribution and activity-dependent regulation in mammalian visual cortex. Vis Neurosci 22:1-18
Ongwijitwat, Sakkapol; Wong-Riley, Margaret T T (2005) Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons? Gene 360:65-77
Ongwijitwat, Sakkapol; Wong-Riley, Margaret T T (2004) Functional analysis of the rat cytochrome c oxidase subunit 6A1 promoter in primary neurons. Gene 337:163-71
Bai, Xuetao; Wong-Riley, Margaret T T (2003) Neuronal activity regulates protein and gene expressions of GluR2 in postnatal rat visual cortical neurons in culture. J Neurocytol 32:71-8
Wong-Riley, Margaret T T; Jacobs, Paulette (2002) AMPA glutamate receptor subunit 2 in normal and visually deprived macaque visual cortex. Vis Neurosci 19:563-73

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