F. M. Kirby Neurobiology Center | Boston Children's Hospital | Harvard Medical School

Distinct channels of visual information. We take a biophysical approach to investigating the mammalian visual system, primarily by applying electrophysiological and optical techniques to in vitro neural tissue. We compare neural circuits within and across species to learn how mechanisms are diversified to serve distinct needs.

Regulation of physiology and behavior by light. The first circuit is primarily responsible for driving "non-image" visual functions such as the regulation of sleep, circadian rhythms, and hormone levels. It employs unusual photoreceptors: retinal output cells that sense light directly, using a molecule called melanopsin. We study the mechanisms of signal generation by these intrinsically photosensitive retinal ganglion cells, and interpret them within the context of downstream circuits in the retina and brain.

Origin of high-resolution vision. The second circuit is that of the fovea, a structure that initiates most of our conscious, visual awareness. The fovea encodes the image in exceptional detail. Although the anatomical specializations that support this performance are well appreciated, there has been little exploration at the level of cellular physiology. We seek to bridge this gap in knowledge.

Health relevance. The intrinsically photosensitive retinal ganglion cells, by serving as the principal regulator of the circadian clock, are responsible for setting the normal pattern of gene regulation throughout the body; circadian dysregulation has been implicated in jet lag, metabolic disorders, cancer, and other ailments. The fovea is destroyed in macular degeneration, a leading cause of blindness in developed nations. Understanding the normal physiology of these systems provides a first step toward maintaining and repairing them.

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Depicted in the image above (left panel) is a cell in the mammalian retina that is unusual in being both a photoreceptor and an output neuron. Here, we have filled one of these intrinsically photosensitive retinal ganglion cells (ipRGCs, the brightest cell in the image) with a soluble tracer.
The tracer has diffused into a number of other neurons (small, dimly-labeled cells). The function of this local network is presently unknown. Also shown is an electrophysiological recording from another ipRGC (right panel). The cell fires action potentials in response to a brief pulse of light (light monitor below trace) despite being isolated pharmacologically from the retinal network. The mechanism by which the cell proceeds from photon capture to electrical signaling remains largely unclear. Intriguingly, the mechanism is more typical of invertebrate photoreceptors than vertebrate ones, even though this is a vertebrate cell.