Parallel retinal and circadian signalling channels organise mouse hypothalamic activity

Abstract Background Mammalian physiology exhibits pronounced daily changes, canonically under control of a primary clock in the suprachiasmatic nucleus (SCN). Retinal signals align robust diurnal rhythms in SCN output that are commonly viewed as acting to suppress daytime activity in hypothalamic effector sites regulating physiological state. The co-occurrence of retinal projections across such hypothalamic targets could also allow for more direct light-dependent increases in their activity, but the impact of such projections and how they combine with SCN-derived signals remains unexplored. Results We employ a combination of electrical and visual stimulation, in and ex vivo multielectrode recordings, c-Fos mapping and other neuroanatomical investigations to assess circadian and retinal influences on hypothalamic activity. We find a diversity of cell populations across the midline hypothalamus that receive SCN-derived inhibitory and/or excitatory responses of retinal origin and display divergent circadian activity patterns ex vivo. These properties align with the occurrence of melanopsin-dominated visual responses in vivo and the distribution of hypothalamic retinal projections. Accordingly, c-Fos mapping reveals discrete hypothalamic subregions dominated by circadian, light or both types of signals. Conclusions Together, our data establish surprisingly extensive light-dependent activity across the anterior midline hypothalamus that challenges an SCN-dominant model of daily physiological control and reveals potential new substrates for adaptive and disruptive effects of environmental light.