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Quantitative immuno-electron microscopic analysis of nuclear respiratory factor 2 alpha and beta subunits: Normal distribution and activity-dependent regulation in mammalian visual cortex
- MARGARET T.T. WONG-RILEY, SHOU JING YANG, HUAN LING LIANG, GANG NING,, PAULETTE JACOBS
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- Journal:
- Visual Neuroscience / Volume 22 / Issue 1 / January 2005
- Published online by Cambridge University Press:
- 05 April 2005, pp. 1-18
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The macaque visual cortex is exquisitely organized into columns, modules, and streams, much of which can be correlated with its metabolic organization revealed by cytochrome oxidase (CO). Plasticity in the adult primate visual system has also been documented by changes in CO activity. Yet, the molecular mechanism of regulating this enzyme remains not well understood. Being one of only four bigenomic enzymes in mammalian cells, the transcriptional regulation of this enzyme necessitates a potential bigenomic coordinator. Nuclear respiratory factor 2 (NRF-2) or GA-binding protein is a transcription factor that may serve such a critical role. The goal of the present study was to determine if the two major subunits of NRF-2, 2α and 2β, had distinct subcellular distribution in neurons of the rat and monkey visual cortex, if major metabolic neuronal types in the macaque exhibited different levels of the two subunits, and if they would respond differently to monocular impulse blockade. Quantitative immuno-electron microscopy was used. In both rats and monkeys, nuclear labeling of α and β subunits was mainly over euchromatin rather than heterochromatin, consistent with their active participation in transcriptional activity. Cytoplasmic labeling was over free ribosomes, the Golgi apparatus, and occasionally the nuclear envelope, signifying sites of synthesis and possible posttranslational modifications. The density of both subunits was much higher in the nucleus than in the cytoplasm for all neurons examined, again indicating that their major sites of cellular action is in the nucleus. In both layer IVC and supragranular puffs of the macaque visual cortex, the expression of both NRF-2α and β was higher in medium-sized, non-pyramidal (type C and C-like) cells previously shown to have higher CO activity than small, type A and A-like cells with low CO activity. Pyramidal, type B cells in puffs had intermediate levels of CO as well as NRF-2α and β labeling. Monocular impulse blockade induced a greater reduction of NRF-2 labeling in type C/C-like than type A/A-like cells. These results substantiate and extend our previous findings that NRF-2 is constitutively active in adult primate and rat visual cortical neurons, that it is expressed more strongly in metabolically more active neurons, and that its level is directly regulated by neuronal activity, the blockade of which imposes a greater down-regulation of this transcription factor in metabolically more active than less active neurons.
AMPA glutamate receptor subunit 2 in normal and visually deprived macaque visual cortex
- MARGARET T.T. WONG-RILEY, PAULETTE JACOBS
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- Journal:
- Visual Neuroscience / Volume 19 / Issue 5 / September 2002
- Published online by Cambridge University Press:
- 12 November 2002, pp. 563-573
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Glutamate and its various receptors are known to play an important role in excitatory synaptic transmission throughout the CNS, including the primary visual cortex. Among subunits of the AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid), subunit 2 (GluR2) is of special significance because it controls their Ca2+ permeability. In the past, this subunit has been studied mostly in conjunction with other AMPA subunits. The present study sought to determine if GluR2 alone has a distinct laminar distribution in the normal macaque visual cortex, and if its pattern correlated with that of cytochrome oxidase (CO) under normal and monocularly deprived conditions. In the normal adult cortex, GluR2 immunoreactivity (ir) had a patchy distribution in layers II/III, in register with CO-rich puffs. GluR2-ir highlighted the upper border of layer II, the lower border of layer IV (previously termed IVCβdark) and, most prominently, layer VI. Labeled neurons were primarily of the pyramidal type present in the upper border and lower half of layer VI, layers II/III, and scattered in layers V and upper IVB. Labeled nonpyramidal cells were large in layer IVB and small in IVCβdark. Notably, the bulk of CO-rich layers IVC and IVA had very low levels of GluR2-ir. At fetal day 13, however, GluR2 labeling showed a honeycomb-like pattern in layer IVA not found in the adult. A fragment of GluR2 cDNA was generated from a human cDNA library, and in situ hybridization revealed an expression pattern similar to that of GluR2 proteins. After 1–4 weeks of monocular impulse blockade with tetrodotoxin (TTX), alternating rows of strong and weak GluR2-ir in layers VI and II/III appeared in register with CO-labeled dark and light ocular dominance columns in layer IVC and puffs in II/III, respectively. Our results indicate that various cortical layers are differentially influenced by glutamate. The bulk of the major geniculate-recipient layers IVC and IVA have low levels of GluR2, presumably favoring synaptic transmission via Ca2+-permeable glutamate receptors. GluR2 plays a more important role in supragranular and infragranular layers, where the initial geniculate signals are further modified and are transmitted to other cortical and subcortical centers. The maintenance of GluR2 in these output layers is governed by visual input and neuronal activity, as monocular impulse blockade induced a down-regulation of this subunit in deprived ocular dominance columns.