Modulation of glycinergic synaptic transmission in the trigeminal and hypoglossal motor nuclei by the nitric oxide-cyclicGMP signaling pathway.

In a previous work we found that nitric oxide (NO) and cyclicGMP (cGMP) inhibit glutamatergic synaptic transmission in trigeminal motoneurons (MnV). Here we study the actions of the NO/cGMP signaling pathway on glycinergic synaptic transmission in trigeminal and hypoglossal motoneurons (MnXII) in brain stem slices of neonatal rats. Glycinergic inhibitory postsynaptic currents (IPSCs) were recorded in MnV by stimulation of the supratrigeminal nucleus (SuV) and in MnXII by stimulation of the nucleus of Roller. The NO donor DETA/NONOate (DETA/NO) reduced the amplitude of the IPSC to 58.1±4.2% of control values in MnV. In the presence of YC-1, a modulator of guanylate cyclase that acts as a NO sensitizer, lower and otherwise ineffective concentrations of DETA/NO induced a reduction of the IPSC to 47.2±15.6%. NO effects were mimicked by 8 bromo cyclicGMP (8BrcGMP). They were accompanied by an increase in the paired pulse facilitation (PPF) and in the failure rate of evoked IPSCs. 8BrcGMP did not modify the glycinergic currents elicited by exogenous glycine. In MnXII the IPSCs were also reduced by NO donors and 8BrcGMP to 52.9±6.3% and 45.9±4% of control values, respectively. In these neurons, but not in MnV, we also observed excitatory postsynaptic actions of NO donors. We propose that the differences between the two motor pools may be due to a differential development of the nitrergic system in the two nuclei. Our data show that NO, through its second messenger cGMP, reduces inhibitory glycinergic synaptic transmission in both MnV and MnXII. For MnV, evidence in favor of presynaptic inhibition of glycine release is presented. Given our previous data together with the current results, we propose that the NO/cGMP signaling pathway participates pre- and postsynaptically in the combined regulation of MnV and MnXII activities in motor acts in which they participate.

The possible additional role of the cystic fibrosis transmembrane regulator to motoneuron inhibition produced by glycine effects.

In the present work we study the contribution of the chloride channel of the Cystic Fibrosis Transmembrane Regulator (CFTR) in the postsynaptic inhibition of somatic motoneurons during rapid-eye-movement (REM) sleep atonia. Postsynaptic inhibition of motoneurons is partially responsible for the atonia that occurs during REM sleep. Disfacilitation is an additional mechanism that lowers motoneuron excitability in this state. Postsynaptic inhibition is mediated by the release of glycine from synaptic terminals on motoneurons, and by GABA that plays a complementary role to that of glycine. In this work we look in brain stem motoneurons of neonatal rats at a mechanism unrelated to the actions of glycine, GABA or to disfacilitation which depends on the chloride channel of the CFTR. We studied the presence of CFTR by immunocytochemistry. In electrophysiological experiments utilizing whole cell recordings in in vitro slices we examined the consequences of blocking this chloride channel. The effects on motoneurons of the application of glycine, of the application of glibenclamide (a CFTR blocker) and again of glycine during the effects of glibenclamide were studied. Glycine produced an hyperpolarization, a decrease in motoneuron excitability and a decrease in input resistance, all characteristic changes of the postsynaptic inhibition produced by this neurotransmitter. Glibenclamide produced an increase in input resistance and in motoneurons' repetitive discharge as well as a shift in the equilibrium potential for chloride ions as indicated by the displacement of the reversal potential for glycinergic actions. In motoneurons treated with glibenclamide, glycine produced postsynaptic inhibition but this effect was smaller when compared to that elicited by glycine in control conditions. The fact that blocking of the CFTR-chloride channel in brain stem motoneurons influences glycinergic inhibition suggests that this channel may play a complementary role in the glycinergic inhibition that occurs during REM sleep.