Autophagy in the retina affects photoreceptor synaptic plasticity and behavior

Abstract

The visual system is a sensory system which is sensitive to light and detects photic stimuli. It plays many important functions, such as vision, circadian clock entrainment and regulation of sleep-wake behavior. The interconnection between the visual system and clock network is precisely regulated. The outer layer of the visual system called the retina, is composed of opsin-based photoreceptors that, in addition to visual information, provide photic information for the circadian clock, which in turn, regulates daily rhythms, such as activity and sleep patterns. The retina houses its own circadian oscillators (belonging to peripheral oscillators), however, they are also controlled by the main clock (pacemaker). Photoreceptor cells show many clock and light-dependent rhythms, such as the rhythms in synaptic plasticity or rhodopsin turnover, but their precise regulation is still not completely understood. In this study, we provided evidence that one of the mechanisms involved in the regulation of retinal rhythms is autophagy. We showed that autophagy is rhythmic in photoreceptors, with a specific daily pattern of autophagosome levels in different cells. Moreover, our data suggest that rhythmic autophagy-dependent degradation of the presynaptic protein Bruchpilot or photosensitive rhodopsin is involved in the regulation of daily rhythms observed in the retina. In effect, autophagy disruption in the photoreceptors, which affects photic signal transmission to the main clock neurons, causes changes in sleep level and pattern.