Samer Hattar is an associate professor in the Department of Biology and holds a joint appointment in the Department of Neuroscience at the School of Medicine. He received his PhD from the University of Houston in Texas. From 2000-2004, Professor Hattar did his postdoctoral work at Johns Hopkins University School of Medicine and the Howard Hughes Medical Institute. His research focuses on light effects on circadian rhythms, sleep, mood and learning.
Vision beyond image formation: The role of melanopsin cells in regulating mammalian physiology
Our ability to observe and enjoy the beauty of a spring blossom or the fascinating fall colors is critically dependent on the ability of our retina to capture photons and then signal this information all the way to the visual cortex. Image formation uses the classical photoreceptor cells, known as rods and cones. Rods and cones contain photopigments (light-absorbing pigments), which are composed of a protein moiety (opsin, which is a G-protein coupled receptor) and a vitamin-A-based chromophore (11-cis-retinal). Rhodopsin and cone opsins capture the light energy (photons) and transduce it into an electrical signal, which is the currency understood by neurons. Interestingly, in humans, light impacts many physiological functions including sleep and mood that are important for quality of life. Our interest pertains to understanding the cellular, molecular and behavioral pathways by which light influences several light-dependent physiological functions independent of image formation. These light-dependent functions include adjusting our internal biological clock to the outside solar day, constricting our pupils to control the amount of light passing through to the retina and the direct light alerting signals.
For many years, it was assumed that rods and cones are the only photoreceptors capable of detecting light in the mammalian retina. However, research from several laboratories uncovered a third type of photoreceptor cell in the mammalian retina. These cells express the photopigment melanopsin first identified by Ignacio Provencio and colleagues, and were shown to be intrinsically photosensitive by David Berson and colleagues. Robert Lucas and colleagues were the first to show conclusively (yet indirectly) that the melanopsin cells absorb light maximally at different wavelength than those of rods and cones. We in close, fruitful and continuing collaborations with Robert Lucas and David Berson have shown that these cells target specifically non-image-forming centers in the brain including the suprachiasmatic nucleus (center for the circadian pacemaker), and the olivary pretectal nucleus (the area responsible for pupil constriction) among many others. The main purpose of our research is to understand both the mode of action of these newly identified photoreceptors, and the individual contributions of the rods, cones and these novel photoreceptors in signaling light for non-image-forming visual functions. Recently, we genetically engineered mice where the Diphtheria toxin (aDTA) is specifically expressed in melanopsin-containing retinal ganglion cells. We showed that the Opn4aDTA animal have normal image functions but lack the ability for circadian photoentrainment. These studies are interesting because they indicate that the ability to form images does not allow animals to detect light for a seemingly simple function such as ajusting the circadian clock to the outside solar day. A wonderful review by Russ Van Gelder in Nature Neuroscience describes the implications of this study (Van Gelder RN. How the clock sees the light. Nat Neurosci. 2008 Jun;11(6):628-30.)
Chen SK, Chew KS, McNeill DS, Keeley PW, Ecker JL, Mao BQ, Pahlberg J, Kim B, Lee SC, Fox MA, Guido W, Wong KY, Sampath AP, Reese BE, Kuruvilla R, Hattar S. 2013. Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment. Neuron 77:503-515.
Comment in Pinto-Teixeira F., Desplan C. 2013. Dying to entrain: regulating ipRGC spacing. Dev Cell 24:338-340.
Legates, T.A., Altimus, C.M., Wang, H., Lee, H.K., Yang, S., Zhao, H., Kirkwood, A., Weber, E.T., Hattar, S. 2012. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491:594-598.
Comment in Lewis S (2013) Circadian rhythms: Light hits mood head-on. Nat Rev Neurosci 14:2-3. and Monteggia LM, Kavalali ET (2012) Circadian rhythms: Depression brought to light. Nature 491:537-538.
Schmidt, T., Chen, S.K., and Hattar, S. 2011. Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci, Epub ahead of print.
Chen, S.K., Badea, T.C., and Hattar, S. 2011. Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs. Nature 476, 92-5. doi: 10.1038/nature10206.
McNeill, D.S., Sheely, C.J., Ecker, J.L., Badea, T.C., Morhardt, D., Guido, W., and Hattar, S. 2011. Development of melanopsin-based irradiance detecting circuitry. Neural Development 6:8.
Altimus, C.M., Güler, A.D., Alam, N.M., Arman, A.C., Prusky, G.T., Sampath, A.P., Hattar, S. 2010. Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities. Nat Neurosci 13:1107-12.
Ecker, J.L., Dumitrescu, O.N., Wong, K.Y., Alam, N.M., Chen, S.K., LeGates, T., Renna, J.M., Prusky, G.T., Berson, D.M., Hattar, S. 2010. Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron 67, 49-60.
Altimus, C.M., LeGates, T.A., Hattar, S., 2009. Circadian and Light effects on Mood Regulation. Chapter in Mouse Models of Mood and Anxiety disorders, NeuroMethods. 42: 47-65. Humana Press, New York, NY.
Badea, T.C., Cahill, H., Ecker, J., Hattar, S., Nathans, J., 2009. Distinct roles of transcription factors brn3a and brn3b in controlling the development, morphology, and function of retinal ganglion cells. Neuron, 61, 852-64.
Altimus, C.M., Güler, A.D., Villa, K.L., McNeill, D.S., Legates, T.A., Hattar, S., 2008. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation. PNAS, 105, 19998- 20003.
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., Zhao, H., Hankins, M.W., Berson, D.M., Lucas, R.J., Yau, K.-W., Hattar, S., 2008. Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature, 453, 102-5.
Hattar, S., Kumar, M., Park, A., Tong, P., Tung, J., Yau, K.-W., Berson, D.M. 2006. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol. 497:326-49.
Hattar, S., Lucas, R.J., Mrosovsky, N., Thompson, S., Douglas, R.H., Hankins, M.W., Lem, J., Biel, M., Hofmann, F., Foster, R.G., and Yau, K.-W., 2003. Melanopsin and Rod–Cone Photoreceptive Systems Account for All Major Accessory Visual Functions in Mice. Nature 424, 76-81.
Lucas, R.J., Hattar, S., Takoa, M., Berson, D.M., Foster, R.G., and Yau K.-W. 2003. Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice. Science 299:245-247.
Hattar, S., Liao, H.-W., Takoa, M., Berson, D.M., and Yau, K.-W. 2002. Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity. Science 295, 1065-70.
Hattar, S., Lyons, L.C., Dryer, L., and Eskin, A. 2002. Circadian Regulation of the Transcription Factor, ApC/EBP in the Eye of Aplysia Californica. J Neurochem 83:1401-11.
Liu, Q.R., Hattar, S., Endo, S., MacPhee, K., Zhang, H., Cleary, L.J., Byrne, J.H., and Eskin, A. 1997. A Developmental Gene (Tolloid/BMP-1) is Regulated in Aplysia Neurons by Treatments that Induce Long-Term Sensitization. J Neurosci. 17, 755-764.