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David Berson, Ph.D., Massachusetts Institute of Technology, 1980

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David Berson

Title: Professor of Medical Science
Department: Neuroscience
Section: Molecular and Cellular Neurobiology.

David_Berson@brown.edu
401-863-2555, 401-863-7751

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Overview | Research | Grants/Awards | Teaching | Publications

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.

Biography

I am a 'lifer' at Brown, having done undergraduate and postdoctoral studies here before joining the faculty in 1985. I conduct basic research on the structure and function of the visual system and teach neuroanatomy and neurophysiology to undergraduate, graduate and medical students. My lab studies what the eye tells the brain. We focus on retinal neurons that send information directly to visual centers of the brain. There are roughly twenty types of these output cells, each with anatomical and physiological features matched to the requirements of specific visual behaviors. We recently discovered that some of them are true photoreceptors; they respond directly to light like rods and cones and synchronize the biological clock and constrict the pupil. We also study retinal output cells that stabilize our view of the world. We want to understand how these cells work and how their signals are used by the brain.

Research Description

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.

Awards

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

Affiliations

Society for Neuroscience

American Association for the Advancement of Science

Association for Research in Vision and Ophthalmology

Society for Research on Biological Rhythms

Funded Research

Current grants

NIH RO1 EY12793
National Eye Institute, National Institutes of Health
"Structure and function of mammalian ganglion cells"
4/1/2003-3/31/2008
$1,250,000
Role: principle investigator

NIH 1 R01 EY017137-01
National Eye Institute, National Institutes of Health
"Biology of photosensitive ganglion cells"
2/1/2006 – 1/31/2011
$1,125,000 direct costs over 5 years
Role: Principle investigator


Completed grants

NSF 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

Teaching Experience

My main teaching commitment is as director of an advanced undergraduate laboratory course in neuroanatomy (Neur 1650). I also teach a seminar at either the graduate or undergraduate level in the neurobiology of the visual system (Neur 1940 or Neur 2120). 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.

Courses Taught

  • Structure of the Nervous System (BN0165)
  • Topics in Neuroscience (BN0194)

Selected Publications

  • Weng, S., Estevez, M.E. and Berson, D.M. Mouse ganglion-cell photoreceptors are driven by the most sensitive rod pathway and by both types of cones. PLoS One 8(6): e66480, 2013(2013)
  • Van Hook, M.J., Wong, K.Y. and Berson, D.M. Dopaminergic modulation of ganglion-cell photoreceptors in rat. Eur. J. Neurosci. 35(3-4): 507-518, 2012.(2012)
  • Estevez, M.E., Fogerson, P.M., Ilardi, M.C., Borghuis, B.G., Chan, E., Weng, S., Auferkorte,O.N., Demb, J.B., and Berson, D.M. Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. J. Neurosci. 32(39):13608-13620, 2012(2012)
  • Wong, K.Y. and Berson, D.M. Ganglion-cell photoreceptors and non-image-forming vision. In: Adler's Physiology of the Eye, 11th edition, Kaufman, P.L., Alm, A., Levin, L.A., Nilsson, S.F.E., Ver Hoeve, J.N. and Wu, S.M. (eds). London, Elsevier. (2011).(2011)
  • Renna, J.M., Weng, S.,. and Berson, D.M. Bidirectional interactions between ganglion-cell photoreceptors and retinal waves. Nature Neuroscience 14(7): 827-829, 2011.(2011)
  • Osterhout, J., Josten, N, Pan, F., Yamada, J., Wu, C., Nguyen, P., Panagiotakos, G., Inoue, T., Volgyi, B., Bloomfield, S., Barres, B.A., Berson, D.M., Feldheim, D.A., and Huberman, A.D. Cadherin-6 promotes axon-target matching in a non-image-forming visual circuit. Neuron 71(4):632-639, 2011.(2011)
  • Berson, D.M., Castrucci, A.M. and Provencio, I. Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice. J. Comp. Neurol. 518:2405-2422, 2010.(2010)
  • Ecker, J.L., Dumitrescu, O.N., Wong, K.Y., Alam, N., Chen, S-K, LeGates, T., Renna, J.M., Prusky, G., Berson, D.M. and Hattar, S. Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron 67(1):49-60, 2010. [PMCID: PMC2904318](2010)
  • Van Hook, M.J. and Berson, D.M. Hyperpolarization- activated current (Ih) in ganglion-cell photoreceptors. PLoS One 5(12):e15344, 2010. [PMCID: PMC3004865](2010)
  • Dumitrescu, O.N., Pucci, F.G., Wong, K.Y. and Berson, D.M. Ectopic ON bipolar cell synapses in the OFF sublamina of the inner plexiform layer: contacts with dopaminergic amacrine cells and melanopsin ganglion cells. J. Comp. Neurol. 517(2), 226-244, 2009.(2009)
  • Weng, S., Wong, K.Y. and Berson, D.M. Circadian modulation of melanopsin-driven light response in rat ganglion-cell photoreceptors. J. Biol. Rhythms. 24: 391-402, 2009.(2009)
  • Isayama, T., O'Brien, B.J., Ugalde, I., Muller, J.F., Frenz, A., Aurora, V., Tsiaras, W. and Berson, D.M. Morphology of retinal ganglion cells in the ferret (Mustela putorius furo). J. Comp. Neurol. 517(4), 459-480, 2009.(2009)
  • Graham, D.M. Wong, K.Y., Shapiro, P., Frederick, C., Pattabiraman, K., and Berson, D.M. Melanopsin ganglion cells use a membrane-associated rhabdomeric phototransduction cascade. J. Neurophysiol. 99:2522-2532, 2008.(2008)
  • Güler, A.D., Ecker, J.L., Lall, G.S., Haq, S., Altimus, C.M., Liao, H.-W., Barnard, A.R., Cahill, H., Badea, T.C., Hankins, M.W., Berson, D.M., Lucas, R.J., Yau, K.-W., and Hattar, S. Melanopsin ganglion cells are the principal conduits for rod/cone non-image forming vision. Nature 453, 102-105, 2008.(2008)
  • Zhang, D-Q., Wong, K., Sollars, P., Berson, D., Pickard, G. and McMahon, D. Intra-retinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons. Proc. Natl. Acad. Sci. USA 105(37), 14181-14186, 2008(2008)
  • Wong, K.Y., Dunn, F.A., Graham, D.M., and Berson, D.M. Synaptic influences on rat ganglion-cell photoreceptors. J Physiol. 582(Pt 1):279-96, 2007. Epub 2007 May 17.(2007)
  • Berson, D.M. Phototransduction in ganglion-cell photoreceptors. Pflugers Arch. 454(5):849-55, 2007. Epub 2007 Mar 10.(2007)
  • Berson, D.M. Retinal ganglion-cell types and their central projections. In: The Senses: A Comprehensive Reference. R. Masland (ed.), Oxford, UK (in press).(2007)
  • Wong, K.Y., Graham, D.M. and Berson, D.M. The retina-attached SCN slice preparation: An in vitro mammalian circadian visual system. J. Biol. Rhythms 22(5):400-10, 2007(2007)
  • Hattar, S., Kumar, M., Park, A., Tong, P., Tung, J., Yau, K.-W., and Berson, D.M. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J. Comp. Neurol. 497: 326-349, 2006(2006)
  • Qiu, X., Kumbalasiri, T., Carlson, S.M., Wong, K.Y., Krishna, V., Provencio, I., and Berson, D.M. Induction of photosensitivity by heterologous expression of melanopsin. Nature 433(7027):745-9, 2005(2005)
  • Wong, K.-Y., Dunn, F.A. and Berson, D.M. Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells. Neuron 48(6): 1001-1010, 2005(2005)
  • O'Brien, B.J., Richardson, R., and Berson, D.M. Inhibitory network properties shaping the light evoked responses of cat alpha retinal ganglion cells. Visual Neurosci. 20, 351-361, 2003.(2003)
  • Berson, D.M. Strange vision: ganglion cells as circadian photoreceptors. Trends in Neurosci. 26: 314-320, 2003(2003)
  • Rollag, M.D., Berson, D.M., Provencio, I. Melanopsin, ganglion cell photoreceptors, and mammalian entrainment. J. Biol. Rhythms 18(3): 227-234, 2003.(2003)
  • Lucas, R.J., Hattar, S., Takao, M., Berson, D.M., Foster, R.G. and Yau, K.-W. Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science, 299: 245-247, 2003.(2003)
  • Hattar, S., Liao, H.-W., Takao, M., Berson, D.M. and K.-W. Yau Melanopsin-containing retinal ganglion cells: architecture, projections and intrinsic photosensitivity. Science, 295:1065-1070, 2002.(2002)
  • Berson, D.M., Dunn, F., and Takao, M. Phototransduction by retinal ganglion cells that set the circadian clock. Science, 295:1070-1073, 2002.(2002)
  • O'Brien, B.J., Isayama, T., Richardson, R., and Berson, D.M. Intrinsic physiological properties of cat retinal ganglion cells. J. Physiol. [London] 538.3: 787-802, 2002.(2002)