In the developing retina, melanopsin ganglion cells are the first functional photoreceptors and play an important role in the proper wiring of the visual system from retina to brain. In fact, for the first ten days of life, they are the sole soure of light information to the brain because the bipolar cells which link rods and cones to ganglion cells are not yet mature. In other words, the outer retina is functionally disconnected from the inner retina until postnatal day 10 (P10). We have recently documented a surprising new observation in mouse retina that many immature melanopsin ganglion cells extend their dendrites during the first week of life not only to the conventional location in the inner plexifor layer, but also all the way out to the outer plexiform layer, where in the mature retina, rods and cones synapse onto bipolar cells. We have shown that these melanopsin ganglion cell Complex Outer Retinal Dendrites (CORDs) can be found in close association with cone axon terminals and express post-synaptic density marker 95, suggestive of direct synaptic contact. We have shown that some CORDs persist into adulthood. Thus, CORDs may represent a novel anatomical circuit in the mammalian retina connecting the outer retina to inner retina early in development and bypassing the conventional cone-to- bipolar-cell pathway. However, the functional significance of this circuit is unknown. The goal of this study is to determine the anatomical and physiological properties of this unique circuit and to determine its functional significance in the developing mouse retina. This work is novel because it challenges the canonical view of how melanopsin ganglion cells influence visual system development and proposes a new circuit by which cones may influence the brain far earlier than previously recognized.
Melanopsin ganglion cells have been implicated in a wide range of functions relevant to human health and disease, including circadian disturbances, acute effects on alertness and sleep, neuroendocrine disruption with attendant cancer risk, seasonal affective disorder and light exacerbation of migraine headaches. This research seeks to explore a novel melanopsin ganglion cell retinal circuit in early visual system development.
