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Journal of Neuroscience, Vol 13, 1784-1792, Copyright © 1993 by Society for Neuroscience
Developmental cues modulate GABAA receptor subunit mRNA expression in cultured cerebellar granule neurons
CE Beattie and RE Siegel
Department of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
The developmental expression of mRNAs encoding the GABAA receptor was
analyzed in the rat cerebellar cortex and in cultured cerebellar granule
neurons. Our studies in vivo reveal that the alpha 1-, beta 2-, and gamma
2-subunit mRNA levels in the cerebellar cortex rise dramatically during the
second post-natal week, a period temporally correlated with extensive
cerebellar maturation. To determine if these increases were preprogrammed
or dependent on extrinsic factors, we examined subunit mRNA expression in
granule cell cultures prepared at embryonic day 19 (E19) and postnatal day
10 (P10), immature and mature stages of cerebellar development,
respectively. In E19 cultures, the alpha 1, beta 2, and gamma 2 GABAA
receptor subunit mRNAs were present and their levels remained constant over
the 21 d culture period. These results suggest that GABAA receptor gene
expression is not intrinsic to the immature granule cells. A different
pattern was found in P10 cultures where the three subunit mRNAs were
initially present at levels approximately sixfold higher than those found
at E19. The beta 2- and gamma 2-subunit mRNAs remained constant for 4 d and
then increased sixfold between 4 and 7 d in culture. The magnitude and time
course of these increases were similar to the developmental changes that
occurred in vivo. Thus, our findings raise the possibility that signals
encountered during development are necessary to induce GABAA receptor
subunit mRNA expression. Moreover, these cues have been received by granule
neurons prior to P10.(ABSTRACT TRUNCATED AT 250 WORDS)
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