Orexinergic signaling mediates light-induced neuronal activation in the dorsal raphe nucleus

Abstract

Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy.

Neural mechanism for hypothalamic-mediated autonomic responses to light during migraine

“…They expand the scope of retinohypothalamic projections described previously (50)(51)(52)(53). In the context of the present study, it is tempting to propose that modulation of these peptidergic hypothalamic neurons by light, which, at best, is incompletely documented (54)(55)(56), may trigger some of the affective, autonomic, and hypothalamic symptoms. Specifically, altered dopaminergic activity can facilitate anger and irritability (57)(58)(59)(60), fear, panic, anxiety, and stress (61), altered oxytocinergic activity can reduce stress, anxiety, and fear and facilitate the relaxing, calming, soothing, and happy affects (62,63); altered orexinergic, MCHergic, and histaminergic activity can facilitate the perception of sleepiness and hunger (64-66), altered vasopressinergic activity can facilitate thirst (67), and many of these peptidergic neurons can promote yawning (68,69), salivation (70,71), lacrimation, nasal congestion, and rhinorrhea (64).…”

Low-intensity treadmill exercise and bright light upregulate brain-derived neurotrophic factor expression and intracellular signaling pathway in rat hippocampus and cerebral cortex

“…Light received by the retina stimulates hypothalamic orexinergic neurons in the hypothalamic suprachiasmatic nucleus (SCN) and in the serotonergic nucleus in the dorsal raphe (DRN; Adidharma et al 2012). The SCN is a principal circadian clock and orexin is a neuropeptide regulating the sleep/wake cycle.…”

Hypothalamic dopaminergic neurons in an animal model of seasonal affective disorder

“…ICC was carried out as in previous studies [1, 7] using the primary antibodies TH (1:5000, sc-7847, Santa Cruz) or SST (1:10,000, sc-13099, Santa Cruz). Sections were then processed with the avidin-biotin-immunoperoxidase (ABC) technique using DAB as the chromogen.…”

“…Furthermore, we found that hypothalamic neurons containing the neuropeptide orexin are likely to play a role in mediating the effects of light on mood and anxiety. In grass rats, orexin neurons show light-induced activation following acute light exposure [1], and also respond to chronic changes in lighting condition, such that daytime light deficiency leads to a reduction in the number of orexin-expressing neurons [7]. Additionally, treating grass rats housed in summer-like bright light conditions with a selective orexin receptor 1 (OX1R) antagonist induced depression- and anxiety-like behaviors [7].…”