Neural-circuit architecture underlying non-image-forming visual functions

Abstract

Perceiving and responding to environmental cues underpins survival and cognition. Light, emerging as one of the most ancient and powerful signals, has shaped life on Earth for billions of years. In mammals, light information is primarily detected by retinal photoreceptors: rods, cones, and intrinsically photosensitive retinal ganglion cells. While rods and cones enable image-forming vision, evolution has preserved and extended evolutionarily ancient yet critical non-image-forming visual functions, including circadian photoentrainment, pupillary light reflexes, and light-mediated modulation of metabolism, mood, and neurodevelopment. Although non-image-forming visual functions have been partially characterized in humans and model organisms, our understanding of the neural circuit mechanisms by which light orchestrates diverse behavior remains fragmented. The discovery of ipRGCs, combined with recent advances in systems neuroscience tools, has yielded critical breakthroughs in three domains: (1) light information encoding within photoreceptors, (2) systematic mapping of retinofugal pathways, and (3) central mechanisms of light-regulated physiological functions. These advances have progressively unraveled causal relationships between non-image-forming visual functions and their underlying eye-brain circuitry. This review summarizes groundbreaking progress in the three domains discussed above, highlighting key unresolved questions in the field.