The nervous system extracts and encodes different features the visual world to accomplish specific tasks. Spotting a familiar face in a crowd requires different information than hitting a fastball or judging the ripeness of fruit from its color. Different "channels" of visual information emerge already at the retinal level and are then routed to distinct visual centers of the brain. We seek to understand how retinal cells and circuits process and filter visual information in specific channels, and how these signals are used by the brain to shape appropriate visual behaviors.

The visual system of the brain is highly parallel in its architecture. This is clearly evident in the outputs of the retina, which arise from neurons called ganglion cells. Work in our lab has shown that mammalian retinas contain more than a dozen distinct types of ganglion cells. Each type appears to filter the retinal image in a unique way and to relay this processed signal to a specific set of targets in the brain. My students and I are working to understand the meaning of this parallel organization through electrophysiological and anatomical studies. We record from light-responsive ganglion cells in vitro using the whole-cell patch method. This allows us to correlate directly the visual response properties, intrinsic electrical behavior, synaptic pharmacology, dendritic morphology and axonal projections of single neurons. Other methods used in the lab include neuroanatomical tracing techniques, single-unit recording and immunohistochemistry. We seek to specify the total number of ganglion cell types, the distinguishing characteristics of each type, and the intraretinal mechanisms (structural, electrical, and synaptic) that shape their stimulus selectivities. Recent work in the lab has identified a bizarre new ganglion cell type that is also a photoreceptor, capable of responding to light even when it is synaptically uncoupled from conventional (rod and cone) photoreceptors. These ganglion cells appear to play a key role in resetting the biological clock. It is just this sort of link, between a specific cell type and a well-defined behavioral or perceptual function, that we seek to establish for the full range of ganglion cell types.

My research concerns the structural and functional organization of retinal ganglion cells, the output cells of the retina whose axons make up the optic nerve. Ganglion cells exhibit great diversity both in their morphology and in their responses to light stimuli. On this basis, they are divisible into a large number of types (>15). Each ganglion-cell type appears to send its outputs to a specific set of central visual nuclei. This suggests that ganglion cell heterogeneity has evolved to provide each visual center in the brain with pre-processed representations of the visual scene tailored to its specific functional requirements. Though the outline of this story has been appreciated for some time, it has received little systematic exploration. My laboratory is addressing in parallel three sets of related questions: 1) How many types of ganglion cells are there in a typical mammalian retina and what are their structural and functional characteristics? 2) What combination of synaptic networks and intrinsic membrane properties are responsible for the characteristic light responses of individual types? 3) What do the functional specializations of individual classes contribute to perceptual function or to visually mediated behavior? To pursue these questions, we label retinal ganglion cells by retrograde transport from the brain; analyze in vitro their light responses, intrinsic membrane properties and synaptic pharmacology using the whole-cell patch clamp method; and reveal their morphology with intracellular dyes.

Recently, we have discovered a novel ganglion cell in rat retina that is intrinsically photosensitive. These ganglion cells exhibit robust light responses even when all influences from classical photoreceptors (rods and cones) are blocked, either by applying pharmacological agents or by dissociating the ganglion cell from the retina. These photosensitive ganglion cells seem likely to serve as photoreceptors for the photic synchronization of circadian rhythms, the mechanism that allows us to overcome jet lag. They project to the circadian pacemaker of the brain, the suprachiasmatic nucleus of the hypothalamus. Their temporal kinetics, threshold, dynamic range, and spectral tuning all match known properties of the synchronization or "entrainment" mechanism. These photosensitive ganglion cells innervate various other brain targets, such as the midbrain pupillary control center, and apparently contribute to a host of behavioral responses to ambient lighting conditions. These findings help to explain why circadian and pupillary light responses persist in mammals, including humans, with profound disruption of rod and cone function. Ongoing experiments are designed to elucidate the phototransduction mechanism, including the identity of the photopigment and the nature of downstream signaling pathways. In other studies, we seek to provide a more detailed characterization of the photic responsiveness and both morphological and functional evidence concerning possible interactions with conventional rod- and cone-driven retinal circuits. These studies are of potential value in understanding and designing appropriate therapies for jet lag, the negative consequences of shift work, and seasonal affective disorder.

Current grants

NIH RO1 EY12793
National Eye Institute, National Institutes of Health
"Structure and function of mammalian ganglion cells"
2/1/2014-6/30/2024
Role: Principle investigator


Completed grants

NIH 1 R01 EY017137-01
National Eye Institute, National Institutes of Health
"Biology of photosensitive ganglion cells"
9/1/2011 -  – 8/31/2015
Role: Principle investigatorNSF BNS 841156

National Science Foundation
"Infrared vision in snakes"
1984-1985
$151,800
Role: co-principle investigator

PHS 1 S15 DK39381-01
National Institutes of Health
"Biomedical Research Support Grant"
1986
$4,222
Role: principle investigator

NIH RO1 EY06108
National Eye Institute, National Institutes of Health
"Visual circuitry of the superior colliculus"
1986-1990
$169,289
Role: principle investigator

NIH RO1 EY06108
National Eye Institute, National Institutes of Health
"Visual circuitry of the superior colliculus"
1990-1994
$253,453
Role: principle investigator

PHS 1 S15 CA53754-01 -
National Institutes of Health
" Biomedical Research Support Grant "
1990
$8,972
Role: principle investigator

NIH RO1 EY06108
National Eye Institute, National Institutes of Health
"Visual circuitry of the superior colliculus"
1995-1999
$540,682
Role: principle investigator


NIH RO1 EY12793
National Eye Institute, National Institutes of Health
"Structure and function of mammalian ganglion cells"
2/1/2000-1/31/2004
$791,922 (direct + indirect)
Role: principle investigator

see Publications
 

Magna Cum Laude, Brown University, 1975

National Science Foundation Individual Predoctoral Fellowship, 1975-78

National Institutes of Health Individual Postdoctoral Fellowship, 1980-83

National Science Foundation Travel Awardee, 1984

Alfred P. Sloan Research Fellowship, 1988-92

Sidney A. Fox and Dorothea Doctors Fox Professor of Ophthalmology and Visual Sciences, 2004-present

Chair, Biology and Disease of the Posterior Eye Study Section, National Institutes of Health 2006-2008

Fellow, American Association for the Advancement of Science, 2009-present 

Boycott Award, FASEB Scientific Research Conference, Retinal Neurobiology and Visual Processing  2014

Presidential Faculty Award, Brown University, 2014

Friedenwald Award;  Association for Research in Vision and Ophthalmology 2015

 

 

Society for Neuroscience

American Association for the Advancement of Science

Association for Research in Vision and Ophthalmology

Society for Research on Biological Rhythms

My main teaching commitment is as director of an advanced undergraduate laboratory course in neuroanatomy (Neur 1650).In addition, I periodically present guest lectures in other courses, including the medical school neuroscience course (BI 3650), which I co-directed for many years.