PROJECT SUMMARY A sharp retinal image is essential for accurately encoding the visual world. The focal length of the eyes' optics can be adjusted within a fraction of a second to bring object of interest into sharp focus, a process called “accommodation”. On longer timescales, hours to months, a sharp retinal image is made possible when the axial length of the eye grows to match the refractive power of the optics, a process called “emmetropization”. In order to respond appropriately, accommodation and emmetropization require the retina to detect the sign and magnitude of image defocus. It is well established that the major optical cue that signals the sign of defocus is longitudinal chromatic aberration (LCA). LCA is due to the stronger refraction of short than long wavelength light. The identity of the neurons in the retina that detect LCA signals, and how they relay the signals to the down-stream mechanisms that control eye growth and accommodation, remains one of the great outstanding puzzles in sensory neurobiology. This proposal aims to identify the retinal neurons that respond to LCA. We will use multi-photon calcium imaging to simultaneously measure responses from tens to hundreds of neurons within an area of retina under photopic adaptation levels. Patterned, chromatic images will be used to identify candidate defocus neurons. The somas of the neurons will then be targeted for single-cell whole-cell recordings to measure in detail the receptive field properties and to recover the morphology. We will also measure responses to natural scenes rendered with and without LCA calculated for the optics of the eye. Identification LCA-sensitive neurons will lay the groundwork for future studies aimed at determining how these retinal neurons ultimately control accommodation and emmetropization. These insights may also provide clues as to the origin of the mysterious, continuing increase in the prevalence of myopia and perhaps lead to development of mitigative strategies.