Axonal and synaptic transformations of melanopsin retinal ganglion cell output

Harvard Medical School, Boston MA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Animals rely on visual information to interact with their environment. In contrast to visual perception, other visual functions benefit from a temporally and spatially blurred version of the surroundings – one that is sensitive to overall illumination (irradiance) instead of image detail. In mammals, these functions rely on intrinsically photosensitive retinal ganglion cells (ipRGCs) which sense light directly due to their expression of the photopigment melanopsin. There is evidence that the M1 type of ipRGC is required for a wide range of non-image-forming visual functions such as setting of circadian phase, control of the pupil, and even regulation of mood. These mechanisms of physiological control appear to be dependent on a measure of irradiance. Indeed, our lab has shown that M1s are exceptionally well-suited to encode environmental irradiance thanks to efficient temporal integration and population level responses that span the physiological range of light intensities. That said, previous studies of M1 ipRGCs have focused on the somatodendritic compartment. The hypothesis driving this proposal is that axonal and synaptic specializations make M1s even more effective at encoding and transmitting irradiance information than is currently appreciated. Aim 1 will explore the functional consequences of axonal melanopsin expression. M1 axons can travel long distance (>1mm) within the retina where they are subject to natural light stimulation. My preliminary data suggest that the axons can sense light and generate action potentials independently of the soma. I will explore the ways in which this axonal photosensitivity augments the output of M1s. Aim 2 will explore how synaptic properties further transform the output of M1s and dictate how they drive downstream circuits. M1s have been identified as vital for two regulatory behaviors in particular: circadian control (mediated by the suprachiasmatic nucleus; SCN) and pupillary control (mediated by the olivary pretectal nucleus; OPN). M1s control circadian phase on slow timescales (hours to days) but control the pupil on fast timescales (seconds to minutes). I will explore the features of the M1 synapse, in combination with those of the postsynaptic cells of the SCN and OPN, that enable M1s to drive these qualitatively and quantitatively disparate behaviors. Together, these experiments will inform our understanding of how ipRGCs encode and transmit photic information and will add to our basic understanding of the biophysical mechanisms underlying neuronal signaling.