Cognitive, Behavioral, and Systems NeuroscienceResearch PaperSleep-waking discharge profiles of dorsal raphe nucleus neurons in mice
Highlights
▶The mouse dorsal raphe neurons show a marked cellular and functional heterogeneity. ▶The mouse dorsal raphe nucleus contains both waking-active and sleep-active neurons. ▶The dorsal raphe neurons have different topographic organizations within the nucleus.
Section snippets
Animals and surgery
All procedures were approved by the University of Lyon 1 Animal Care Committee, the standards of which meet those of the European Communities Council Directive of 24 November 1986 (86/609/EEC). All efforts were made to minimize the number of animals used and their suffering.
Twenty-five male adult C57BL/6 mice (Janvier SAS, St. Berthevin, France; 29–35 g at the time of surgery) were anesthetized using a mixture of 0.8 mg/ml of ketamine (Imalgene 1000, Merial, Lyon, France) and 1 mg/ml of
General characteristics of DR neurons
Fig 2 illustrates the distribution of 5-HT, TH, ChAT, or GAD67-immunoreactive neurons in, and around, the mouse DR, which is divided into the medial (DRM) and lateral (DRL) DR, the DRM being further divided along the rostrocaudal axis into the three regions of rostral (DRMr), middle (DRMm), and caudal (DRMc) (Fig. 1, Fig. 2A–F). As shown in Fig 2A–F, and as reported by previous authors (Bonnavion et al., 2010, Daszuta and Portalier, 1985; Fu et al., 2010, Hioki et al., 2010, Ishimura et al.,
Discussion
For the first time in non-anesthetized, head-restrained mice, we have recorded a total of 407 single units throughout the DR, which contains 5-HT neurons, during the complete wake-sleep cycle. The mouse DR neurons showed a marked heterogeneity, consisting of a large proportion (52.0%) of W-active neurons, many sleep-active (24.8%) or W/PS-active (18.4%) neurons, and a few state-unrelated neurons (4.7%). W-active, W/PS-active, and sleep-active neurons were distinguished from each other by either
Conclusions
This study in mice revealed a marked cellular and functional heterogeneity of DR neurons. Serotonergic and nonserotonergic DR neurons have different topographic organizations within the DR, and, as either local or projection neurons, could modulate behavioral states by playing different roles in sleep/wake state regulation.
Acknowledgments
This study was supported by INSERM U1028, CNRS UMR5292, and Claude Bernard University. We thank Professor H. Kimura (Shiga, Japan) for his generous gift of the anti–5-HT antiserum and Gérard Guidon for his help with the electronics.
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