Neurotransmitter-mediated control of neuronal firing in the red nucleus ofthe rat: Reciprocal modulation between noradrenaline and GABA

The electrical activity of neurons from the red nucleus, a mesencephalic st ructure involved in motor control, is under the influence of several neurot ransmitters released from afferent fibers and/or from local interneurons. W e have investigated the combined effects of gamma-aminobutyric acid (GABA) and noradrenaline (NA), both present at high levels in the red nucleus, on the firing activity of single rubral neurons recorded extracellularly in vi vo on anesthetized adult rats. NA inhibited the bring activity of a large p art of rubral neurons and induced excitatory or biphasic inhibitory/excitat ory effects in a smaller group of cells. Neuronal firing was also inhibited by GABA in all the cells studied. When the effect of GABA was tested durin g continuous applications of NA, the magnitude of GABA response was modifie d in 58% of the cells: the effect of GABA was potentiated by NA in half of the responding neurons and was decreased in the remaining half. NA-induced potentiation of GABA response was mimicked by the alpha(2)-adrenoceptor ago nist clonidine and was abolished by the alpha(2)-adrenoceptor antagonist yo himbine. On the other side, the decrease of GABA response was reproduced by the beta-adrenoceptor agonist isoprenaline and was blocked by timolol, an antagonist of beta-adrenoceptors. Neuronal firing activity was reduced by n ipecotic acid, an inhibitor of GABA reuptake mechanism, and was instead inc reased during application of the GABA(A) receptor antagonist bicuculline, s uggesting that rubral neurons in vivo were under tonic control by endogenou s GABA. Both the inhibitory and the excitatory effects of NA were reduced i n time presence of nipecotic acid and were instead potentiated during appli cation of bicuculline, suggesting that NA responses were modified by endoge nous GABA. Taken together, our results indicate a reciprocal modulation bet ween the effects of GABA and NA on neuronal firing activity in the red nucl eus of the rat: GABA depresses the responsiveness of rubral neurons to NA, whereas NA is able either to potentiate or to decrease the effects of GABA by activation of alpha(2)- and beta-adrenoceptors, respectively. The functi onal significance of such interaction, as well as the possible implication in diseases affecting motor control,will be discussed. (C) 2000 Academic Pr ess.