DEVELOPMENTAL-CHANGES IN THE EXPRESSION OF GAMMA-AMINOBUTYRIC ACID(A)BENZODIAZEPINE RECEPTOR SUBUNIT MESSENGER-RNAS IN THE MURINE INFERIOROLIVARY COMPLEX

The pharmacological and physiological properties of ligand-gated ion c hannels are dependent on their subunit composition; spontaneously occu rring changes in subunit composition during neuronal development may r esult in dramatic functional differences between embryonic and adult f orms of the receptor complex. In the present study, in situ hybridizat ion with antisense cRNA probes was used to examine the subunit composi tion of the gamma-aminobutyric acid(A)/benzodiazepine (GABA(A)/BZ) rec eptor in the developing inferior olivary complex. This receptor is tho ught to be a pentameric chloride channel comprised of selected alpha, beta, gamma, delta, and rho subunits, the majority of which have sever al isoforms: alpha(1-6), beta(1-4), gamma(1-4), and rho(1,2). Among th e 13 subunit variants present in the mammalian central nervous system, alpha(2-5), beta(3), and gamma(1,2) mRNAs are expressed at significan t levels in the inferior olivary complex. Two clearly different tempor al patterns of GABA(A)/BZ receptor subunit mRNA expression were observ ed: The expression of alpha(3), alpha(5), beta 3, and gamma 2 mRNAs wa s at a peak during embryonic and early postnatal development followed by rapid down-regulation thereafter. Conversely, alpha(2), alpha(4), a nd gamma(1) mRNA expression was very low or absent during early develo pment, and a pronounced increase was observed at the end of postnatal week 1. These studies suggest that there are developmental changes in the subunit composition of the GABA(A)/BZ receptor in inferior olivary neurons. These changes in subunit expression, which occur during a pe riod of major alterations in afferent and efferent synaptic connection s, may subserve a change in the role of GABA from its function as a ne urotrophic factor to that of an inhibitory neurotransmitter. (C) 1995 Wiley-Liss, Inc.