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Journal of Neuroscience, Vol 14, 2236-2259, Copyright © 1994 by Society for Neuroscience
Lamina-specific expression and activity-dependent regulation of seven GABAA receptor subunit mRNAs in monkey visual cortex
MM Huntsman, PJ Isackson and EG Jones
Department of Anatomy and Neurobiology, University of California, Irvine 92717.
Seven monkey-specific GABAA receptor subunit cDNAs were isolated and
cloned; radioactive cDNA and cRNA probes derived from them were used for
Northern blot analysis and in situ hybridization histochemistry of the
primary visual cortex (area 17), with comparative observations on other
cortical areas. cDNAs corresponding to alpha 1, alpha 2, alpha 4, alpha 5,
beta 1, beta 2, and gamma 2 GABAA receptor subunits were isolated and had
sequences unique to the monkey but recognized mRNAs of distinct molecular
weights consistent with those reported in other species. mRNAs for the
alpha 1, beta 2, and gamma 2 subunits were expressed at much higher levels
in area 17 than in motor, somatosensory, or temporal association cortex,
possibly reflecting the greater density of GABA cells and synapses in area
17. In areas 17 and 18, each of the seven subunit mRNAs showed individually
distinct patterns of laminar distribution. alpha 1, beta 2, and gamma 2
subunit mRNAs, which are thought to form the basis of receptors with the
full range of classical GABAA receptor properties in the adult, were
particularly enriched in layers II-III, IVC, and VI of area 17, following
patterns of receptor distribution previously demonstrated by radioligand
binding and immunocytochemistry. alpha 2, alpha 4, alpha 5, and beta 1
transcripts had quite different localization patterns that did not match
the antoradiographic or immunocytochemical receptor localization patterns.
alpha 2 and alpha 5 subunit mRNAs, which are thought to be the subunits
mainly expressed in development, were enriched in layer VI and the
underlying white matter, possibly reflecting the involvement of receptors
formed from alpha 2 and alpha 5 polypeptides in trophic interactions in the
cortical subplate zone during development of the cerebral cortex. Following
8-21 d periods of monocular deprivation induced by intravitreal injection
of TTX, levels of alpha 1, beta 2, and gamma 2 subunit mRNAs were
substantially reduced in deprived ocular dominance columns of layer IVC in
area 17. The effect was greatest for the alpha 1 subunit; for both alpha 1
and gamma 2 subunit mRNAs, it extended into deprived rows of cytochrome
oxidase-identified periodicities in other layers. Apart from the alpha 5
subunit mRNA, which showed reduced levels in layer VI, the other subunit
mRNAs were unaffected by monocular deprivation. These results demonstrate
the heterogeneity of GABAA receptor subunit expression in a complex,
multilaminar cortical area. They suggest that receptors with different
functional properties may be assembled from different combinations of
subunit polypeptides in different layers and show that subunit expression
is differentially regulated under activity-dependent conditions.
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