Histaminergic circadian modulation of mouse retinal output in vivo

How is the retinal visual processing affected by the behavior and internal states of an animal? The structure and function of the vertebrate retina have been extensively studied ex vivo across species. Recent studies, however, demonstrated that the retina operates differently in vivo, especially in an awake condition. Using in vivo recording methods in mice together with chemogenetic tools, here we identified the effects of the histaminergic system on retinal visual responses in the context of the circadian rhythm. Specifically, we found histaminergic modulation of the retinal response kinetics, but not the firing rate, via the projection from histidine decarboxylase-positive neurons in the tuberomammillary nucleus of the posterior hypothalamus. Furthermore, pharmacologically blocking a postsynaptic histamine receptor (H1) facilitated the response kinetics, while blocking the H3 receptor – an autoreceptor that presynaptically inhibit histamine release – slowed down the response latency. Finally, we examined the circadian effects and found that the retinal response latencies were shorter during day time than night time. Given that mice are nocturnal animals, and that histaminergic neurons fire more during subjective day time (i.e., objective night), we suggest that the retinal responses are faster in the absence of histamine, and this will be beneficial for animals to respond faster to potential threats when animals are asleep. Because visual processing in the brain fully relies on the signals from the retina, characterization of the retinal operation in vivo is indispensable to better understand how the visual system works.