Il ruolo delle proiezioni istaminergiche nel grigio periacqueduttale ventrolaterale

The level of arousal influences the spontaneous and visually directed activity of the visual system. This effect has been detected in the primary visual cortex, lateral geniculate nucleus and superior colliculus of mice. Moreover, arousal has been shown to influence vision much earlier, in the firing of some retinal ganglion cells, according to recordings from retinal axons in the optic tract. Regardless of retinal illumination, their activity was influenced by running speed (i.e. locomotion) and pupil size which are used as proxies for arousal. The histaminergic system in the brain, originating in the tuberomammillary nucleus (TMN), is involved in many physiological, sensory, motor and behavioural functions, such as endocrine homeostasis (feeding, body temperature regulation, energy homeostasis), nociception, locomotion, sleep-wake cycle, arousal, as well as memory and cognition. Sparse retinopetal axons from TMN reach the inner plexiform layer of the retina, modulating the responses of a variety of inner retinal neurons. The histaminergic neurons also project to numerous other regions in the brain including the ventrolateral periaqueductal grey (vlPAG). Previous studies show that vlPAG is involved in locomotion, defensive behaviour and antinociception; however, it remains unclear how histerminergic neurons affect vlPAG, hence an animal’s behaviour. We hypothesised that histaminergic neurons mediate the correlation between an animal’s locomotion and the retinal ganglion cell activity by innervating vlPAG and the retina by innervating both regions at the same time. To test this, we explored whether activating histaminergic projections to vlPAG has an effect on locomotion, thus modulating the arousal level. Specifically, the activation of histaminergic projections was achieved with the use of optogenetic methods. Apart from that, anterograde and retrograde tracing experiments have been performed to demonstrate the innervation of histaminergic projections into vlPAG.