Signal Generation and Processing in the Retinohypothalamic Pathway

PROJECT SUMMARY This proposal concerns the broad question of how relevant information is extracted from the environment and formatted according to animal needs. We focus on the process by which light synchronizes the circadian clock with the solar day and thus sets appropriate patterns of physiology and gene expression throughout the body. In mammals, this process requires neurons in the eye that sense light directly using a molecule called melanopsin and indirectly by receiving input from retinal circuitry. These melanopsin neurons wire into the principal circadian clock—the suprachiasmatic nucleus of the brain—via the retinohypothalamic pathway. We have developed new methods of investigating this pathway ex vivo under naturalistic conditions. First is a means of identifying melanopsin neurons that maintains their maximum photosensitivity (both intrinsic and extrinsic). Second is an experimental preparation in which the retina and suprachiasmatic nucleus retain functional connectivity. Using these methods, we will investigate how photic information arises in the retina and acutely drives neurons of the suprachiasmatic nucleus. We will focus on how this process produces a representation of the overall light intensity, which reflects the sun’s position in the sky and is used by the clock to maintain alignment with the day/night cycle. Specifically, we will ask how retinal and suprachiasmatic circuitry smooth away rapid fluctuations in light intensity, which tend to be uninformative for the clock (being caused, for example, by a passing cloud or flash of lightning). We expect that this work will provide knowledge of how neural processing is tailored to specific tasks and how environmental cues interact with internal states according to animal needs.