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

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

3.1. Double immunostaining procedure

The procedure used for retrograde tracing with cholera-toxin B subunit (CTb) and anterograde tracing with PHAL has been described in detail previously (Luppi et al., 1990; 1995; Peyron et al., 1996). The high sensitivity of CTb allowed us to demonstrate pathways not seen before using HRP, WGA-HRP or fluorescent tracers.

3.2. Afferent projections to the LC

Following iontophoretic injections of CTb into the core of the LC, we observed a substantial number of retrogradely labeled cells in the lateral and dorsal paragigantocellular nuclei as previously described (Aston-Jones et al., 1986).

We also saw a substantial number of retrogradely labeled neurons in (1) the preoptic area dorsal to the supraoptic nucleus, (2) areas of the posterior hypothalamus, (3) the Kölliker-Fuse nucleus, (4) and the mesencephalic reticular formation. Fewer labeled cells were also observed in other regions including the hypothalamic paraventricular nucleus, nucleus raphe dorsalis, median raphe nucleus, dorsal part of the periaqueductal gray, the area of the noradrenergic A5 group, the lateral parabrachial nucleus and the caudoventrolateral reticular nucleus.

These results were confirmed and extended with anterograde transport of CTb or PHAL. Injections of these tracers in the lateral paragigantocellular nucleus, preoptic area dorsal to the supraoptic nucleus, the posterior hypothalamic areas, the ventrolateral part of the periaqueductal gray, the Kölliker-Fuse nucleus yielded a substantial to large number of labeled fibers in the nuclear core of the LC.

In conclusion, our results indicate that the LC receives afferents from a very large number of structures from the forebrain to the medulla. Failure to demonstrate these afferents in earlier works (Cedarbaum and Aghajanian, 1978; Aston-Jones et al., 1986) was certainly due to the poor sensibility of the retrograde tracers used (HRP, WGA-HRP and fluorogold).

3.2.1. Origin of the Glycinergic inputs to the LC

Following CTb injections centered on the LC, a large number of double-labeled cells were observed in the ventrolateral and lateral parts of the periaqueductal gray where they represented a small proportion of the CTb+ cells (Fig. 4A). At the same level, a substantial number of CTb/gly+ neurons were also detected in the mesencephalic reticular formation. A moderate number of double-labeled neurons were also seen in the raphe magnus, gigantocellular alpha, lateral and dorsal paragigantocellular nuclei (Rampon et al., 1996). These results are summarized in Figure 4.

3.2.2. Origin of the GABA-ergic inputs to the LC

Following CTb injections in the LC, many brain regions contained GAD+/CTb+ neurons. A large number of double-labeled cells were localized in the lateral preoptic area, the lateral hypothalamic area, the lateral and ventrolateral parts of the periaqueductal gray and the dorsal paragigantocellular nucleus. A small number of double-labeled cells were also seen in the dorsal hypothalamic area, the tuberomamillary nucleus, the mesencephalic reticular formation, the lateral parabrachial nucleus and the nucleus raphe magnus (Peyron et al., 1995). These results are summarized in Figure 5.

Figure 4


Figure 5

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