Superior Colliculus GABAergic Neurons Are Essential for Acute Dark Induction of Wakefulness in Mice

Sleep is regulated by homeostatic process and circadian clock. Light indirectly modulates sleep by entraining the circadian clock to the solar day. Light can also influence sleep independent of photo-entrainment [1Altimus C.M. Güler A.D. Villa K.L. McNeill D.S. Legates T.A. Hattar S. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation.Proc. Natl. Acad. Sci. USA. 2008; 105: 19998-20003Crossref PubMed Scopus (197) Google Scholar]. An acute light exposure could induce sleep, and an acute dark pulse could increase wakefulness in nocturnal animals [1Altimus C.M. Güler A.D. Villa K.L. McNeill D.S. Legates T.A. Hattar S. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation.Proc. Natl. Acad. Sci. USA. 2008; 105: 19998-20003Crossref PubMed Scopus (197) Google Scholar, 2Lupi D. Oster H. Thompson S. Foster R.G. The acute light-induction of sleep is mediated by OPN4-based photoreception.Nat. Neurosci. 2008; 11: 1068-1073Crossref PubMed Scopus (180) Google Scholar]. The photoreceptors and cell types in the retina that mediate light and dark effects on sleep are well characterized [1Altimus C.M. Güler A.D. Villa K.L. McNeill D.S. Legates T.A. Hattar S. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation.Proc. Natl. Acad. Sci. USA. 2008; 105: 19998-20003Crossref PubMed Scopus (197) Google Scholar, 2Lupi D. Oster H. Thompson S. Foster R.G. The acute light-induction of sleep is mediated by OPN4-based photoreception.Nat. Neurosci. 2008; 11: 1068-1073Crossref PubMed Scopus (180) Google Scholar, 3Muindi F. Zeitzer J.M. Colas D. Heller H.C. The acute effects of light on murine sleep during the dark phase: importance of melanopsin for maintenance of light-induced sleep.Eur. J. Neurosci. 2013; 37: 1727-1736Crossref PubMed Scopus (23) Google Scholar, 4Tsai J.W. Hannibal J. Hagiwara G. Colas D. Ruppert E. Ruby N.F. Heller H.C. Franken P. Bourgin P. Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice.PLoS Biol. 2009; 7: e1000125Crossref PubMed Scopus (167) Google Scholar]. A few studies have explored the brain region involved in acute light induction of sleep. Fos expression and nonspecific lesions suggest that the superior colliculus (SC) may play a role in acute light induction of sleep [2Lupi D. Oster H. Thompson S. Foster R.G. The acute light-induction of sleep is mediated by OPN4-based photoreception.Nat. Neurosci. 2008; 11: 1068-1073Crossref PubMed Scopus (180) Google Scholar, 5Miller A.M. Obermeyer W.H. Behan M. Benca R.M. The superior colliculus-pretectum mediates the direct effects of light on sleep.Proc. Natl. Acad. Sci. USA. 1998; 95: 8957-8962Crossref PubMed Scopus (78) Google Scholar]. In contrast, the brain area and neural circuits mediating acute dark induction of wakefulness are unknown. Here, we demonstrated that retina ganglion cells (RGCs) had direct innervations on the GABAergic neurons in the mouse SC, and the activities of these cells were inhibited by an acute dark pulse, but not influenced by a light pulse. Moreover, ablating SC GABAergic neurons abolished the acute dark induction of wakefulness, but not light induction of sleep. Based on optogenetic and electrophysiological experiments, we found that SC GABAergic neurons formed monosynaptic functional connections with dopaminergic neurons in the ventral tegmental area (VTA). Selective lesions of VTA dopaminergic cells totally abolished acute dark induction of wakefulness without affecting the light induction of sleep. Collectively, our findings uncover a fundamental role for a retinal-SC GABAergic-VTA dopaminergic circuit in acute dark induction of wakefulness and indicate that the dark and light signals affect sleep-wake behaviors through distinct pathways.