GABA(A) BENZODIAZEPINE RECEPTOR ALPHA(6) SUBUNIT MESSENGER-RNA IN GRANULE CELLS OF THE CEREBELLAR CORTEX AND COCHLEAR NUCLEI - EXPRESSION IN DEVELOPING AND MUTANT MICE/
L. Varecka et al., GABA(A) BENZODIAZEPINE RECEPTOR ALPHA(6) SUBUNIT MESSENGER-RNA IN GRANULE CELLS OF THE CEREBELLAR CORTEX AND COCHLEAR NUCLEI - EXPRESSION IN DEVELOPING AND MUTANT MICE/, Journal of comparative neurology, 339(3), 1994, pp. 341-352
The gamma aminobutyric acid(A)/benzodiazepine (GABA(A)/BZ) receptor is
a multisubunit (alpha, beta, gamma, delta, and rho) ligand-gated chlo
ride channel; there are several variants of the alpha, beta, and gamma
subunits, each of which has been localized throughout the central ner
vous system. A large number of GABA(A)/BZ subunit variants are express
ed within the cerebellar cortex. In previous studies from other labora
tories, alpha(6) subunit mRNA has been reported to be present exclusiv
ely in cerebellar granule cells. The developmental expression of alpha
(6) mRNA in cerebellar and cochlear granule cells is of interest becau
se it has been suggested that each of these cell types is derived from
a common precursor pool. The polymerase chain reaction was used to ge
nerate a cDNA fragment encoding a portion of the M3-M4 intracellular l
oop of the alpha(6) subunit of the GABA(A)/BZ receptor. A [S-35] ribop
robe, transcribed from this cDNA fragment, was used to examine the exp
ression of the alpha(6) subunit mRNA by in situ hybridization in devel
oping normal mice and in adult mutant mice with known deficits in syna
ptic circuitry. A strong hybridization signal was observed over the gr
anule 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 labelin
g 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 we
ek 3. In the weaver mutant, alpha(6) labeling was detected in survivin
g granule cells, but not in cerebellar regions devoid of granule cells
. Significant levels of the alpha(6) hybridization signal were also pr
esent in cerebellar granule cells of Purkinje cell degeneration, lurch
er, and staggerer mutants, suggesting that aberrations in synaptic cir
cuitry do not prevent alpha(6) subunit gene expression. Our results de
monstrate that alpha(6) subunit mRNA is not limited to the cerebellum,
but is expressed in other neurons which share a common cellular precu
rsor 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 conn
ections with target neurons.