From pineal photoreception to optogenetics: functional colour opponency based on a pineal bistable opsin

Abstract Most animals sense light through opsins, which are photosensitive G protein–coupled receptors that utilize light information to regulate various physiological functions. In vertebrates, a representative example of such functions is vision, which is based on photoreception by visual opsins expressed in rod and cone photoreceptor cells of the retina. Accumulating photobiological evidence has gradually revealed the significance of the molecular properties of these opsins, as well as those of signal transduction–related molecules such as transducin, rhodopsin kinases, and arrestins, and their collective contribution to the functional characteristics of retinal photoreceptor cells. Furthermore, electrophysiological studies of animal photoreception have demonstrated that pineal-related organs in many vertebrates exhibit photosensitivity. Consequently, these organs are referred to as the “third eye,” in addition to the bilateral eyes. Light responses in pineal-related organs have been electrophysiologically described across various vertebrates, from lampreys to birds. In particular, species ranging from lampreys to lizards commonly exhibit two characteristic types of responses: “achromatic” and “chromatic.” Since the 1990s, genome projects have identified numerous opsin genes in diverse animal species and revealed their remarkable diversity. This has led to rapid advances in the study of “non-visual” opsins and their associated physiological functions. Along with these developments, the opsin repertoire in pineal-related organs has been shown to differ from that in the eyes. In this article, we review electrophysiological evidence of photosensitivity in pineal-related organs and describe the molecular basis underlying this sensitivity. Furthermore, we discuss the role of the pineal-specific opsin parapinopsin, which possesses molecular properties distinct from those of visual opsins, in photoreceptor cells, as well as examples of its application in optogenetics. Overall, this review highlights the molecular and physiological significance of pineal opsins and emphasises their emerging potential in optogenetic applications.