Norepinephrine and REM sleep
Pierre-Hervé Luppi , Christelle Peyron, Claire Rampon, Damien Gervasoni, Bruno Barbagli, Romuald Boissard and Patrice Fort
Rapid Eye Movement Sleep pp. 107-122B.N. Mallick, S. Inoue (Editors) Narosa Publishing House 1999

Table of contents

1. Introduction

2. Effect of the application of gaba and glycine antagonists on the activity of the rat locus coeruleus neurons during sleep

3. Glycinergic and gaba-ergic afferent projections to the locus coeruleus

4. Physiological role of the glycinergic inputs to the LC

5. Physiological role of the gaba-ergic inputs to the LC

6. Conclusions and new hypothesis

4. Physiological role of the glycinergic inputs to the LC

The effect of strychnine indicates the existence of a tonic glycinergic input on LC cells during W, SWS and PS. Further, we found that when the same neuron was recorded during short successive periods of SWS and W during the strychnine effect, its increases in discharge rate was strongly superior during W than SWS. These results indicate that when the tonic inhibition of LC cells by GLY is completely removed by strychnine, the LC cells are still under a specific inhibition by another neurotransmitter during SWS. Further, our results with bicuculline indicate that GABA appears to be this neurotransmitter (see next chapter). Unfortunately, due to the smaller number of LC cells successively recorded during SWS and PS, we were not able to make the same comparison between these two sleep states. However, with the microdialysis technique, Nitz and Siegel (1997) recently found no detectable change in the GLY concentration in the cat LC during SWS and PS as compared to waking values. The glycinergic tonic inhibition might therefore be kept constant across the sleep-waking cycle and control the general excitability of LC neurons. This control could either arise from the major glycinergic input to the LC from the ventrolateral and lateral parts of the periaqueductal gray (CG) and the adjacent mesencephalic reticular formation or the smaller inputs from the lateral paragigantocellular, raphe magnus, dorsal paragigantocellular and gigantocellular alpha nuclei.

Of interest regarding the periaqueductal gray input, Sastre et al. (1996) in cats recently showed that the inactivation of the ventrolateral periaqueductal gray by muscimol (a GABAa agonist) induced a dramatic increase of PS. This result might be explained by the fact that the glycinergic neurons constitute only a minor proportion of the neurons from the ventrolateral periaqueductal gray. The effect seen by Sastre et al. (1996) could therefore be due to the inhibition of other types of neurons (in particular glutamatergic or GABAergic)(Beitz, 1995)

Besides, we observed a small number of glycinergic neurons in the nucleus gigantocellular alpha and the adjacent raphe magnus projecting to the LC. Based on a number of studies in cats, we made the hypothesis that during PS, the monoaminergic neurons and the cranial and spinal somatic motoneurons might be inhibited by a single population of glycinergic neurons located in the magnocellular reticular nucleus (cat's equivalent of gigantocellular alpha and ventral nuclei, Gia and GiV). However, the present results and those we recently obtained on the glycinergic afferents to the motor trigeminal nucleus (Mo5)(Rampon et al, 1996) indicate at least in rats that the GiV provide only a limited glycinergic input to the LC and Mo5 and are therefore unlikely to contain a single population of neurons responsible for the inhibition of monoaminergic and all somatic motoneurons during PS. In fact, in rats, the only motoneurons receiving a strong glycinergic projection from the Gia and GiV are those of the spinal cord as demonstrated by Holstege and Bongers (1991). In view of these results in rats, the cranial motoneurons might be rather inhibited during PS by neurons from the parvocellular and parvocellular alpha reticular nuclei and glycine might not be specifically involved in the inhibition of monoaminergic neurons during sleep. Additional experiments are nevertheless necessary to confirm such conclusion in particular in cats in which it has been shown that the magnocellular but not the parvocellular reticular nuclei contains C-Fos positive cells following long periods of PS induced by carbachol injections in the pons (Yamuy et al., 1993)

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