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Regulation of the GABA(A) receptor gene family during cerebellar ontogeny

by Beattie, Christine Elizabeth

Abstract (Summary)
The developmental expression of mRNAs encoding the GABA A receptor was analyzed in the rat cerebellar cortex and in cultured cerebellar granule neurons using the polymerase chain reaction. Our results in vivo revealed that the ?1, ?2 and ?2 subunit mRNA levels increased dramatically during a period temporally correlated with extensive cerebellar maturation. To determine if these increases were dependent on environmental cues encountered during development, we examined subunit mRNA expression in cerebellar 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 ?1, ?2 and ?2 GABA A receptor subunit mRNAs were present and their levels remained constant over 21 days in culture. A different pattern was found in P10 cultures where the three subunit mRNAs were initially present at levels approximately 6-fold higher than those found at E19. The ?2 and ?2 subunit mRNAs remained constant for 4 days and then increased an additional 6-fold between 4 and 7 days in culture. Thus, our findings indicate that specific signals encountered during cerebellar maturation before P10 may b e necessary to induce GABA A receptor subunit mRNA expression. The possibility that environmental cues modulate GABA A receptor subunit mRNA expression is also supported by our work in vivo. The expression of the ?1, ?2 and ?2 subunit mRNAs was examined in the mutant mouse weaver where the majority of cerebellar granule neurons die before forming synapses with target Purkinje neurons. Analysis of receptor mRNAs revealed that this decrease in excitatory input to Purkinje neurons resulted in a significant decrease (25-60%) in expression of the ?1, ?2 and ?2 subunit mRNAs compared to control Purkinje neurons. To begin to elucidate signals that induce GABA A receptor subunit mRNA expression, E19 granule cells were grown under conditions altering excitability, and neurotransmitter and growth factor concentrations. When granule cells were grown under these conditions there was no significant changes in subunit mRNA levels. Our results suggest that the correct signal has not been tested or that immature neurons may be unresponsive to signals which induce GABA A receptor genes
Bibliographical Information:

Advisor:

School:Case Western Reserve University

School Location:USA - Ohio

Source Type:Master's Thesis

Keywords:gaba a receptor genes cerebellar ontogeny

ISBN:

Date of Publication:01/01/1993

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