CHOLINERGIC CELL EXPRESSION IN THE DEVELOPING RAT MEDIAL SEPTAL NUCLEUS IN-VITRO IS DIFFERENTIALLY CONTROLLED BY GABA(A) AND GABA(B) RECEPTORS

The early appearance and relative abundance of GABAergic neurons in ba sal forebrain cholinergic nuclei like the medial septum suggest that t he maturation of the later developing cholinergic neurons in these nuc lei may be controlled by GABA. To examine this possibility, the effect s of both exogenous GABA and specific GABA receptor agonists, as well as that of endogenous GABA on the phenotypic expression and survival o f the cholinergic neurons in primary cultures from the fetal rat media l septum, were studied. Treatment of these cultures for six days with GABA significantly decreased the enzymatic activity of choline acetylt ransferase (EC 2.3.1.6) (ChAT) in a dose-dependent manner. This respon se to exogenous GABA was blocked by bicuculline, mimicked by muscimol and slightly potentiated by saclofen. Consistent with this latter obse rvation, the GABA(B) receptor agonist, baclofen, dose-dependently incr eased septal ChAT activity. However, while the effect of baclofen on c holinergic expression was lost in the absence of glia, the suppressive effects of GABA or muscimol were more marked. Acetylcholinesterase (E C 3.1.1.7) (AChE) expression in mixed neuronal-glial cultures, was, li ke ChAT activity, increased or decreased in intensity with the inclusi on of baclofen or muscimol, respectively. Although the number of AChE positive neurons in muscimol-treated cultures was significantly lower than that in controls, no changes in neither neuronal nor general cell viability were noted. Finally, as GABA(A) or GABA(B) receptor antagon ists bicuculline and picrotoxin or saclofen, when applied alone to mix ed cultures, increased or decreased ChAT activity, respectively, it ap pears that endogenous GABA, tonically released in the developing septu m, may, via specific receptor types, differentially control the bioche mical maturation of the cholinergic neurons. (C) 1998 Elsevier Science B.V. All rights reserved.