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

The pharmacological and physiological properties of ligand-gated ion channels are dependent on their subunit composition; spontaneously occurring changes in subunit composition during neuronal development may result in dramatic functional differences between embryonic and adult forms of the receptor complex. In the present study, in situ hybridization with antisense cRNA probes was used to examine the subunit composition of the gamma-aminobutyric acid(A)/benzodiazepine (GABA(A)/BZ) receptor in the developing inferior olivary complex. This receptor is thought to be a pentameric chloride channel comprised of selected alpha, beta, gamma, delta, and rho subunits, the majority of which have several isoforms: alpha(1-6), beta(1-4), gamma(1-4), and rho(1,2). Among the 13 subunit variants present in the mammalian central nervous system, alpha(2-5), beta(3), and gamma(1,2) mRNAs are expressed at significant levels in the inferior olivary complex. Two clearly different temporal patterns of GABA(A)/BZ receptor subunit mRNA expression were observed: The expression of alpha(3), alpha(5), beta 3, and gamma 2 mRNAs was at a peak during embryonic and early postnatal development followed by rapid down-regulation thereafter. Conversely, alpha(2), alpha(4), and gamma(1) mRNA expression was very low or absent during early development, 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 period of major alterations in afferent and efferent synaptic connections, may subserve a change in the role of GABA from its function as a neurotrophic factor to that of an inhibitory neurotransmitter. (C) 1995 Wiley-Liss, Inc.