GABA(A)/benzodiazepine receptor α6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei: Expression in developing and mutant mice

L. Varecka, C. H. Wu, A. Rotter, A. Frostholm

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The gamma aminobutyric acid(A)/benzodiazepine (GABA(A)/BZ) receptor is a multisubunit (α, β, γ, δ, and ρ) ligand-gated chloride channel; there are several variants of the α, β, and γ subunits, each of which has been localized throughout the central nervous system. A large number of GABA(A)/BZ subunit variants are expressed within the cerebellar cortex. In previous studies from other laboratories, α6 subunit mRNA has been reported to be present exclusively in cerebellar granule cells. The developmental expression of α6 mRNA in cerebellar and cochlear granule cells is of interest because it has been suggested that each of these cell types is derived from a common precursor pool. The polymerase chain reaction was used to generate a cDNA fragment encoding a portion of the M3-M4 intracellular loop of the α6 subunit of the GABA(A)/BZ receptor. A [35S] riboprobe, transcribed from this cDNA fragment, was used to examine the expression of the α6 subunit mRNA by in situ hybridization in developing normal mice and in adult mutant mice with known deficits in synaptic circuitry. A strong hybridization signal was observed over the granule cell layers of both the cerebellum and cochlear nuclei in adult mice. The signal over the cochlear nuclei appeared after birth toward the end of postnatal week 1, coinciding with the appearance of labeling in the cerebellar cortex. The intensity of the hybridization signal in both regions increased rapidly until postnatal day 14, after which it increased more gradually, reaching adult levels during postnatal week 3. In the weaver mutant, α6 labeling was detected in surviving granule cells, but not in cerebellar regions devoid of granule cells. Significant levels of the α6 hybridization signal were also present in cerebellar granule cells of Purkinje cell degeneration, lurcher, and staggerer mutants, suggesting that aberrations in synaptic circuitry do not prevent α6 subunit gene expression. Our results demonstrate that α6 subunit mRNA is not limited to the cerebellum, but is expressed in other neurons which share a common cellular precursor pool. These data also suggest that these granule cell precursors may be intrinsically programmed to acquire a specific form of the GABA(A)/BZ receptor, irrespective of their final location and lack of connections with target neurons.

Original languageEnglish
Pages (from-to)341-352
Number of pages12
JournalJournal of Comparative Neurology
Volume339
Issue number3
DOIs
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Cochlear Nucleus
Cerebellar Nuclei
Cerebellar Cortex
GABA-A Receptors
Messenger RNA
gamma-Aminobutyric Acid
Cerebellum
Complementary DNA
Ligand-Gated Ion Channels
Neurons
Chloride Channels
Purkinje Cells
Cochlea
Benzodiazepines
In Situ Hybridization
Central Nervous System
Parturition
Gene Expression
Polymerase Chain Reaction

Keywords

  • gamma aminobutyric acid(A)
  • in situ hybridization
  • lurcher
  • Purkinje cell degeneration
  • staggerer
  • weaver

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

GABA(A)/benzodiazepine receptor α6 subunit mRNA in granule cells of the cerebellar cortex and cochlear nuclei : Expression in developing and mutant mice. / Varecka, L.; Wu, C. H.; Rotter, A.; Frostholm, A.

In: Journal of Comparative Neurology, Vol. 339, No. 3, 1994, p. 341-352.

Research output: Contribution to journalArticle

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AU - Wu, C. H.

AU - Rotter, A.

AU - Frostholm, A.

PY - 1994

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