GABA(A) RECEPTOR SUBUNIT MESSENGER-RNA EXPRESSION IN THE WEAVER CEREBELLUM - MODULATION BY CELL-CELL INTERACTIONS

Recent studies have suggested that the developmental expression of GABA(A) receptor subunit mRNAs in cerebellar Purkinje neurons is modulated by cell-cell interacactions. In this population, the levels of mRNAs encoding the alpha 1, beta 2, and gamma 2 subunits increase simultaneously during the second week of postnatal ontogeny, a period temporally coincident with cerebellar maturation and synapse formation. To determine the importance of cell-cell interactions in modulating receptor gene expression, the levels of GABA(A) receptor subunit mRNAs in Purkinje neurons of weaver mice and littermate controls were examined by quantitative in situ hybridization histochemistry. In the weaver mutant most granule neurons die early in postnatal development, thus eliminating the major source of excitatory input to Purkinje cells. Despite this loss, the three subunit mRNAs were expressed in all Purkinje neurons. However, the levels of expression were generally lower in the mutants than in the littermate controls. These results suggest that the onset of GABA(A) receptor gene expression in cerebellar Purkinje neurons occurs in the absence of extensive synapse formation by mechanisms which may be intrinsic to the neurons. In contrast, the absolute level of transcript expression attained appears to be modulated by cell-cell interactions or by other extrinsic cues present in the cerebellar environment.