Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep - PubMed (original) (raw)

Selective activation of the extended ventrolateral preoptic nucleus during rapid eye movement sleep

Jun Lu et al. J Neurosci. 2002.

Abstract

We found previously that damage to a cluster of sleep-active neurons (Fos-positive during sleep) in the ventrolateral preoptic nucleus (VLPO) decreases non-rapid eye movement (NREM) sleep in rats, whereas injury to the sleep-active cells extending dorsally and medially from the VLPO cluster (the extended VLPO) diminishes REM sleep. These results led us to examine whether neurons in the extended VLPO are activated during REM sleep and the connectivity of these neurons with pontine sites implicated in producing REM sleep: the laterodorsal tegmental nucleus (LDT), dorsal raphe nucleus (DRN), and locus ceruleus (LC). After periods of dark exposure that triggered enrichment of REM sleep, the number of Fos-positive cells in the extended VLPO was highly correlated with REM but not NREM sleep. In contrast, the number of Fos-positive cells in the VLPO cluster was correlated with NREM but not REM sleep. Sixty percent of sleep-active cells in the extended VLPO and 90% of sleep-active cells in the VLPO cluster in dark-treated animals contained galanin mRNA. Retrograde tracing from the LDT, DRN, and LC demonstrated more labeled cells in the extended VLPO than the VLPO cluster, and 50% of these in the extended VLPO were sleep-active. Anterograde tracing showed that projections from the extended VLPO and VLPO cluster targeted the cell bodies and dendrites of DRN serotoninergic neurons and LC noradrenergic neurons but were not apposed to cholinergic neurons in the LDT. The connections and physiological activity of the extended VLPO suggest a specialized role in the regulation of REM sleep.

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Figures

Fig. 1.

Fig. 1.

A pair of photomicrographs showing the distributions of Fos-ir cells in the extended VLPO and VLPO cluster in an animal exposed to light (12% REM sleep, A) and in an animal exposed to dark treatment (30% REM sleep, B) during the early part of the sleep cycle. The counting boxes used for the VLPO cluster and the dorsal and medial extended VLPO are shown in B. These sections are approximately at the level of AP −0.5 in Paxinos and Watson (1986).OC, Optic chiasm.

Fig. 2.

Fig. 2.

Correlation (illustrated by solid line) of the number of Fos-ir cells in the extended VLPO and VLPO cluster in light- and dark-treated animals with the amounts of REM sleep or NREM sleep that the animals experienced during the hour before perfusion.

Fig. 3.

Fig. 3.

Photomicrographs showing dual labeling of Fos (brown immunostaining) and galanin mRNA (black silver grains representing in situ hybridization) in the extended VLPO and VLPO cluster. Arrowheads indicate double-labeled cells. Many Fos-ir cells in the extended VLPO and particularly in the VLPO cluster contain galanin mRNA. _A_shows the VLPO complex with boxes that are shown at higher magnification in B–D. Note that these fields are not equivalent to the counting boxes shown in Figure 1.OC, Optic chiasm.

Fig. 4.

Fig. 4.

Camera lucida drawings showing selected injection sites (black solid and dashed lines) of CTB in the region of the DRN (A), LDT (B), and LC (C) as well as four injection sites of PHA-L in the VLPO region (D). Gray shading shows borders of key nuclei;gray lines show other brain structures. Br, Barrington's nucleus; HDB, horizontal limb of the nucleus of the diagonal band of Broca; mlf, medial longitudinal fasciculus; MnRn, median raphe nucleus;OC, optic chiasm; scp, superior cerebellar peduncle; VTg, ventral tegmental nucleus.

Fig. 5.

Fig. 5.

Dual labeling of CTB retrograde transport (brown) and Fos expression (black) in cells within the extended VLPO and VLPO cluster (B,E, H) after the injections of CTB into the central DRN (A, experiment R2049), LDT (D, experiment R1969), and LC (G, experiment R2219), respectively, in the rats exposed to 3 hr of darkness. In B, E, and H, the VLPO cluster is identified by a large arrow and the extended VLPO by a large double-headed arrow. The_rectangular boxes_ identify the fields that are magnified in C, F, and I, respectively. Double-labeled cells in the extended VLPO and VLPO cluster are indicated by small arrows and single CTB labeled cells are indicated by small arrowheads.

Fig. 6.

Fig. 6.

Photomicrographs showing the relationships of anterogradely labeled efferent axons (black) from the extended VLPO and VLPO cluster with neurons in the DRN, LDT, and LC that are stained (brown) for serotonin, choline acetyltransferase, or tyrosine hydroxylase, respectively. In_A_, the efferent terminals concentrate dorsal to the cluster of the cholinergic cells in the LDT. Occasionally we found that terminal boutons were near choline acetyltransferase-immunoreactive neurons such as in B; however careful observation indicated that such boutons were not on the same plane as the cholinergic cell body. In C and D, efferent terminal boutons clearly appose serotonin-immunoreactive neurons in the DRN. E and F show labeled efferent axons apposing tyrosine hydroxylase-immunoreactive neurons in the LC.

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