Elsevier

Brain Research

Volume 987, Issue 1, 10 October 2003, Pages 100-106
Brain Research

Research report
Indirect projections from the suprachiasmatic nucleus to the median preoptic nucleus in rat

https://doi.org/10.1016/S0006-8993(03)03295-5Get rights and content

Abstract

We recently showed, using dual tract-tracing, that the suprachiasmatic nucleus (SCN), the site of the principal circadian clock in mammals, may have indirect projections to the sleep-promoting ventrolateral preoptic nucleus (VLPO) via relays in the medial preoptic area (MPA), dorsomedial hypothalamic nucleus (DMH), and, to a lesser extent, the subparaventricular zone (SPVZ). Here, we found that the injection of the rostral MPA, the periventricular nucleus/medial SPVZ, and the caudal DMH with a mixture of anterograde and retrograde tracers resulted in dense anterograde labeling in the median preoptic nucleus (MnPO), another key sleep-promoting nucleus in the preoptic region. The retrograde labeling in the SCN was evident as previously reported. The injections in either the MPA or the DMH produced similar densities of varicose fibers between the MnPO and the VLPO, while the injections in the SPVZ yielded a greater density of varicose fibers in the MnPO than in the VLPO. These results suggest that the MPA and DMH are potential relay nuclei to mediate SCN output to the MnPO, as well as to the VLPO, for the circadian control of sleep–wake states.

Introduction

The suprachiasmatic nucleus (SCN) in the anterior hypothalamus generates the central circadian signal for virtually all physiological and behavioral functions in mammals, including daily sleep–wake cycles [19], [31]. However, how the SCN reaches the sleep–wake regulatory system to exert circadian influence on the occurrence of sleep and wake states is not well understood. We recently identified several potential indirect neuronal pathways from the SCN to the ventrolateral preoptic nucleus (VLPO) [8], a sleep-promoting nucleus of the preoptic area [23], [27]. The potential relay nuclei in these indirect pathways were the medial preoptic area (MPA), the dorsomedial hypothalamic nucleus (DMH), and to a lesser extent, the subparaventricular zone (SPVZ) [8], all of which have been known to be main targets of SCN efferent projections (reviewed in Refs. [17], [36]).

Recent evidence indicates that the median preoptic nucleus (MnPO), involved in body fluid balance, blood pressure control, and thermoregulation [2], [16], [24], [33], is yet another sleep-promoting nucleus in the preoptic area [15]. Many neurons of the MnPO exhibit c-Fos immunoreactivity in response to spontaneous sleep [9]. The majority of MnPO neurons also begin to increase their discharge rate prior to sleep, and remain active during both non-rapid eye movement (REM) sleep and REM sleep [29]. The MnPO projects to several forebrain and brainstem regions implicated in the regulation of arousal, including monoaminergic cell groups in the brainstem [38], and cholinergic and hypocretin/orexin-containing neurons in the forebrain [10]. This growing evidence for the role of the MnPO in sleep generation prompted us to examine whether the MnPO, like the VLPO, is also positioned to receive SCN output via previously identified main targets of SCN efferent projections [8]. Preliminary results have been published in abstract form [7].

Section snippets

Materials and methods

The present study involved the histological processing and examination of additional sections obtained from the animals used in our previous study [8]. Detailed information on the animals and the experimental procedures for axonal tracer injections and perfusion has been provided [8]. Briefly, under anesthesia, adult male Wistar rats were injected with a mixture of biotinylated dextran-amine (BDA) and cholera toxin subunit B (CTB), or BDA alone, into several known main targets of SCN efferents,

Results

Table 1 summarizes the results of the anterograde labeling in the MnPO in 42 animals used in the present study. The injection sites and the quantitative analysis of the retrograde labeling in the SCN in these cases were adapted from our previous study [8]. The 42 cases were categorized into four groups according to the injection site [8]: MPA (n=10); SPVZ (n=13); DMH (n=12); and PH (n=7).

For a given nucleus to be considered a likely relay nucleus between the SCN and the MnPO, tracer injections

Discussion

The main finding of the present study is that the rostral MPA, the anterior periventricular nucleus/medial SPVZ, and the caudal DMH all receive strong projections from the SCN, and in turn, send dense projections to the MnPO. In addition, the present study confirmed that the rostral MPA, the caudal DMH and, to a lesser extent, the anterior periventricular nucleus/medial SPVZ, also project to the VLPO [8]. These findings suggest that the MPA and DMH may constitute major relay nuclei to mediate

Acknowledgements

We thank Joan Burns for excellent technical assistance. This work was supported by the Canadian Institutes of Health Research Grant (MOP-42553), and The Province of Nova Scotia Department of Health. S.D. was supported by postdoctoral awards from Fondation Singer-Polignac and Nova Scotia Health Research Foundation.

References (38)

  • T.C. Chou et al.

    Afferents to the ventrolateral preoptic nucleus

    J. Neurosci.

    (2002)
  • S. Deurveilher et al.

    Anatomical analysis of indirect efferent pathways of the suprachiasmatic nucleus to wake-related cell groups in rat

    Actas Fisiol.

    (2001)
  • S. Deurveilher et al.

    Indirect pathways from the suprachiasmatic nucleus to hypocretin/orexin-containing, monoaminergic and cholinergic cell groups in rat

    Soc. Neurosci. Abstr.

    (2001)
  • S. Deurveilher et al.

    Indirect projections from the suprachiasmatic nucleus to wake-related neuronal groups in the forebrain and brainstem in rat

    Sleep Suppl.

    (2001)
  • S. Deurveilher et al.

    Indirect projections from the suprachiasmatic nucleus to the median preoptic nucleus: a dual tract-tracing study in rat

    Sleep Suppl.

    (2002)
  • S. Deurveilher et al.

    Indirect projections from the suprachiasmatic nucleus to the ventrolateral preoptic nucleus: a dual tract-tracing study in rat

    Eur. J. Neurosci.

    (2002)
  • H. Gong et al.

    Sleep-related c-Fos protein expression in the preoptic hypothalamus: effects of ambient warming

    Am. J. Physiol.

    (2000)
  • H. Gong et al.

    Projections from the median preoptic nucleus to forebrain arousal systems in rats

    Soc. Neurosci. Abstr.

    (2001)
  • A. Kalsbeek et al.

    GABA receptors in the region of the dorsomedial hypothalamus of rats are implicated in the control of melatonin and corticosterone release

    Neuroendocrinology

    (1996)
  • Cited by (43)

    • Hypothalamus

      2016, The Curated Reference Collection in Neuroscience and Biobehavioral Psychology
    • Neuroanatomy of the extended circadian rhythm system

      2013, Experimental Neurology
      Citation Excerpt :

      There are multiple candidate routes by which the SCN can influence the sleep system or, in turn, be influenced by it. These include connections with the ventrolateral preoptic area (VLPO) (Chou et al., 2002; Deurveilher and Semba, 2003; Novak and Nunez, 2000), possibly with lateral hypothalamic (LH) neurons of the orexin (OX) system (Abrahamson et al., 2001; Schwartz et al., 2011) or through IGL connections with brainstem sleep regulatory nuclei (Morin and Blanchard, 2005). Neither system can be fully understood without knowing the contribution of each.

    View all citing articles on Scopus
    View full text