The Functions Of IpRGC In Image-forming And Non-image-forming Vision

Vision is the most important way for mammals to perceive the world.Visual perception begins with three types of photoreceptors in the mammalian retina:rods,cones,and intrinsically photosensitive retinal ganglion cells(ipRGCs).The ipRGCs,known as non-imaging visual photoreceptors,can be activated by blue light with peak around 480 nm through melanopsin encoded by the gene Opn4.These three types of photoreceptors are responsible for perceiving almost all visual information and mediate different physiological functions.Vision can be divided into two parallel parts:One is image-forming vision,which encodes the features of images such as shape,color,orientation and motion.The other is called non-image-forming vision,which regulates physiological functions at non-conscious level based on the encoding of intensity and duration of illumination.It has long been thought that these two visual functions are separated from the light sensation of retinal photoreceptors:Image-forming vision is mediated solely by rods and cones,with light information first reaching the dorsal lateral geniculate nucleus(dLGN)via the optic nerve and then being transmitted to the primary visual cortex(Ⅵ)for image feature processing.Meanwhile,the non-image-forming vision was thought to be predominantly mediated by ipRGCs,which regulate circadian rhythm,pupillary reflex,and negative emotion through direct projections to multiple nuclei in the thalamus.However,recent studies have shown that ipRGCs also have axonal projection and weak receptive field information input to dLGN,suggesting that ipRGCs may also be involved in the image processing.Studies in the retina have shown that light sensation of ipRGCs(M4 ipRGCs)enhance the visual contrast signal transmitted from rods and cones.However,for mammalian visual systems,the visual cortex is the first center for representing visual features.Therefore,understanding the contribution of ipRGCs to the image coding in the visual cortex is the key to delineating the role of ipRGCs in image-forming vision.In this study,we first demonstrate the visual neuronal circuit of ipRGCs→dLGN→V1 using retrograde transsynaptic tracer tool.Using in-vivo two-photon cortical calcium imaging,we demonstrated that light can activate layer 2/3 neurons of mouse V1 via ipRGCs.Light activation of ipRGCs significantly improves the orientation selectivity of neurons in the layer 2/3 of mice V1,one of the most fundamental features of image processing,including increasing the orientation selectivity index and the neuronal response at preferred orientation,as well as narrowing the tuning width.Furthermore,using Go/NoGo behavioral system,we demonstrated that light activation of ipRGCs improved the orientation discriminability in mice.Above all,we demonstrate that light activation of ipRGCs improve the orientation selectivity of V1 and visual orientation discriminability in mice.It breaks the bias that ipRGCs only mediates non-imaging visual function,and enriches the unknown function of ipRGCs in the regulation of visual image feature coding.On the other hand,the photosensitivity of ipRGCs matured earlier than rods and cones during mammalian retinal development,making them the earliest neurons with photosensitivity after birth.The mammalian brain develops rapidly at early postnatal stage,where visual input is crucial for the establishment of synaptic connections in the cerebral cortex(synaptogenesis).As the only type of functional photoreceptors in the retina at early postnatal stage,ipRGC-mediated light sensation may play an important role in the regulation of synaptogenesis in the cerebral cortex.To this end,by electrophysiological recording and neuronal morphological labeling,we firstly demonstrated that ipRGCs-mediated early light sensation promotes synaptogenesis of multiple cerebral cortices as well as hippocampus.The ipRGCs-mediated light sensation activates oxytocin neurons in the supraoptic(SON)and paraventricular nucleus(PVN)via the ipRGCs→ SONOXT→PVNOXT neural circuits,which consequently increase the levels of oxytocin in cerebrospinal fluid.As one of the key factors of synaptic establishment,oxytocin directly promotes the synaptogenesis of cerebral cortices and hippocampus.What’s more,ipRGCs-promoted brain synaptogenesis at early postnatal stage further enhances the learning ability of mice in adulthood.This study expands the non-imaging visual function of ipRGC during early postnatal stage,elucidating the neural circuit and molecular mechanism as well as the life-long impact of light-promoted early brain synaptogenesis.The study provides a basis for further exploration of the mechanisms by which environmental factors regulate neonatal brain development and suggests that public health research should focus on the lighting environment of infants caring.In summary,this work firstly reveals ipRGCs,the non-image-forming photoreceptors,enhance the V1 orientation selectivity and visual discriminability of mice.On the other hand,it reveals a new non-image-forming function of ipRGCs at early postnatal stage by promoting the synaptogenesis of cerebral cortices and hippocampus,and improving the learning ability at adulthood of mice.This work extends the image-forming and non-image-forming function of ipRGCs,facilitating us to refine the theory of visual information processing and design a more suitable lighting environment for work or infants caring.