Pre- and postsynaptic modulation of glycinergic and gabaergic transmission by muscarinic receptors on rat hypoglossal motoneurons in vitro

The motor output of hypoglossal motoneurons to tongue muscles takes place in concert with the respiratory rhythm and is determined by the balance between excitatory glutamatergic transmission and inhibitory transmission mediated by glycine or GABA. The relative contribution by these transmitters is a phasic phenomenon modulated by other transmitters. We examined how metabotropic muscarinic receptors, widely expressed in the brainstem where they excite cranial motor nuclei, might influence synaptic activity mediated by GABA or glycine. For this purpose, using thin slices of the neonatal rat brainstem, we recorded (under whole-cell patch clamp) glycinergic or GABAergic responses from visually identified hypoglossal motoneurons after pharmacological block of glutamatergic transmission. Muscarine inhibited spontaneous and electrically induced events mediated by GABA or glycine. The amplitude of glycinergic miniature inhibitory postsynaptic currents was slightly reduced by muscarine, while GABAergic miniature inhibitory postsynaptic currents were unaffected. Motoneuron currents induced by focally applied GABA and glycine were depressed by muscarine with stronger reduction in glycine-mediated responses. Histochemical observations indicated the presence of M1, M2 and M5 subtypes of muscarinic receptors in the neonatal hypoglossal nucleus. These results suggest that muscarine potently depressed inhibitory neurotransmission on brainstem motoneurons, and that this action was exerted via preterminal and extrasynaptic receptors. Since the large reduction in inhibitory neurotransmission may contribute to overall excitation of brainstem motoneurons by muscarinic receptors, these data might help to understand the central components of action of antimuscarinic agents in preanesthetic medication or against motion sickness.