Department of Neurobiology, Physiology and Behavior, College of Biological Sciences
Development/plasticity of the mammalian visual system
The research being carried out in my laboratory deals with the developmental neurobiology of the visual system. Currently, three broad issues are being pursued. First, we are interested in the formation of On and Off pathways which signal increments and decrements of light. It is commonly the case, that connections in the brain concerned with coding different features of the sensory world are separated into distinct domains. On/Off retinal pathways represent a prime example of such an organization at a very early level of the neuroaxis. The three cell types involved in this organization (On and Off cone bipolar cells which stratify onto the segregated dendrites of On and Off ganglion cells as well as the processes of cholinergic amacrine cells) have been all well-characterized in the mature retina. Consequently, this system serves as an excellent model for our developmental studies. In the past, we have shown that glutamate-mediated activity is essential for the stratification of On and Off dendrites of retinal ganglion cells. More recently, we demonstrated a highly specific ingrowth pattern of On and Off bipolar cell axons. Remarkably, ganglion cells, the major target of these retinal interneurons were found not to be essential for normal segregation of bipolar cell axons. Currently, we are exploring the involvement of cholinergic amacrine cells in this process. This has motivated us to construct a novel method for immunolesioning cholinergic neurons. A patent for this novel technique has recently been filed by the University of California on our behalf.
A second major focus is the ontogeny of functional properties in retinal ganglion cells. This work mainly involves making whole-cell patch clamp recordings from ganglion cells in embryonic and postnatal retinas. The main goal here is to determine when and how different classes of retinal ganglion cells attain their mature extrinsic as well as intrinsic response properties. For instance, recently we showed that early in development, when the dendrites of ganglion cells are still in a multistratified state, these neurons respond briskly both to the onset and the offset of light. This means that individual ganglion cells are innervated by both On as well as Off cone bipolar cells before these inputs attain their mature segregated state.
A third focus is the formation of specific retinal projection patterns. This work has become increasingly focused on the molecular cues that might underlie the highly precise patterns of projections exhibited by retinal neurons. In particular, we are currently using microarray technologies to identify genes expressed by different classes of retinal ganglion cells that could be responsible for guiding these neurons to make either a crossed or uncrossed projections at the optic chiasm.
Over the years my research program has been generously supported by grants from the NIH, NSF, NIMH, NATO, the Guggenheim Foundation, the Human Frontiers of Science Program. I was pleased to learn that earlier this year the NIH provided my laboratory with another five years of continuous funding. So there is reason to think that we will continue to make progress on the issues described above.
Development/plasticity of the mammalian visual system
Specialties / Focus
- Development and Plasticity
- Systems Neuroscience
Honors and Awards
- 1993 - Japan Society for the Promotion of Science Fellowship
- 1992 - NIH Fogarty International Senior Fellowship
- 1989 - Fellow, American Association for the Advancement of Science
- 1987 - Fellow-in-Residence at the Neurosciences Institute, Rockefeller University, New York
- 1978 - Guggenheim Fellowship
- Society for Neuroscience, AAAS, Sigma Xi, International Brain Research Organization, Association for Research in Vision and Ophthalmology, America Physiological Society
- 1966 BS (Biology) Queens College
- 1970 PhD (Neuropsychology) City University of New York
Chalupa, L. M. and J.S. Werner (Editors). 2003. The Visual Neurosciences, MIT Press, in press.
Gunhan, E., D. van der List, and L.M. Chalupa. 2002. Ectopic photoreceptors and cone bipolar cells in the developing and mature retina. J. Neuroscience, in press.
Gunhan, E., P.V. Choudary, T.E. Landerholm, and L.M. Chalupa. 2002. Depletion of cholinergic amacrine cells by a novel immunotoxin does not perturb the formation of segregated On and Off cone bipolar cell projections. J. Neuroscience, 22: 2265-2273.
Wang, G-Y, L.C. Liets, and L.M. Chalupa. 2001. Unique functional properties of On and Off pathways in the developing mammalian retina. J. Neuroscience, 21:4310-4317.
Gunhan-Agar, E., D. Kahn, and L.M. Chalupa. 2000. Segregation of On and Off bipolar cell axonal arbors in the absence of retinal ganglion cells. J. Neuroscience, 2000, 20, 308-314.
Cook, J. and L.M. Chalupa. 2000. Retinal mosaics: new insights on an old concept. Trends in Neuroscience, 23, 26-34.
Snider, C.J., C. Dehay, H. Kennedy, M. Berland and L.M. Chalupa. 1999. Formation of ey-specific projections in the fetal monkey reflects the loss of retinal fibers rather than the restructuring of axonal processes. J. Neuroscience, 19(1).
Bisti, S., C. Gargini and L.M. Chalupa. 1998. Blockade of glutamate-mediated activity in the developing retina perturbs functional segregation of ON and OFF pathways. J. Neuroscience 18:5019-5025.
Chalupa, L.M. and B.L. Finlay (Eds.). 1998. Development and Organization of the Retina: From Molecules to Function, Plenum Press, New York.
Chalupa, L.M. and C.J. Snider. 1998. Topographic specificity in the retinocollicular projection of the developing ferret: An anterograde tracing study. Journal of Comparative Neurology, 392:35-47.
Wang, G.Y., D.W. Robinson and L.M. Chalupa. 1998. Calcium-activated potassium conductances in retinal ganglion cells of the ferret. Journal of Neurophysiology, 151-158.
Wang, G.Y., G.-M. Ratto, S. Bisti and L.M. Chalupa. 1997. Functional development of intrinsic properties in ganglion cells of the mammalian retina. Journal of Neurophysiology, 2895-2903.
Meissirel, C., K.C. Wikler, L.M. Chalupa and P. Rakic. 1997. Early divergence of functional subsystems in the embryonic primate visual system. Proceedings of the National Academy of Science USA 94:5900-5905.
Robinson, D.W. and L.M. Chalupa. 1997. Intrinsic temporal properties of retinal ganglion cells: a comparison of alpha and beta cells. Current Biology 7:366-374.
Chalupa, L.M., C.J. Snider and M. Kirby. 1996. Topographic organization in the retinocollicular pathway of the fetal cat demonstrated by retrograde labeling of ganglion cells. Journal of Comparative Neurology 368:295-303.
Chalupa, L.M., C. Meissirel and B. Lia. 1996. Specificity of retinal ganglion cell projections in the embryonic rhesus monkey. Perspective of Developmental Neurobiology 3:223-231.
Bodnarenko, S.R., G. Jeyarasasingam and L. M. Chalupa. 1995. Development and regulation of dendritic stratification in retinal ganglion cells by glutamate-mediated afferent activity. Journal of Neuroscience 15:7037-7045.
Hutsler, J.J. and L.M. Chalupa. 1995. The development of neuropeptide Y immunoreactive amacrine and ganglion cells in the pre- and postnatal cat retinal. Journal of Comparative Neurology 361:152-164.
Skaliora, I., D.W. Robinson, R.P. Scobey and L.M. Chalupa. 1995. Properties of K+ conductances in cat retinal ganglion cells during the period of activity-mediated refinements in retinofugal pathways. European Journal of Neuroscience 7:1558-1568.
Miguel-Hidalgo, J.J., K.J. Angelides and L.M. Chalupa. 1995. Distinct temporal patterns of expression of sodium channel-like immunoreactivity during the prenatal development of the monkey and cat retina. European Journal of Neuroscience 7:535-546.
Chalupa, L. M. 1995. The nature /nurture of retinal ganglion cell development. The Cognitive Neurosciences a Handbook for the Field. Ed. M. S. Gazzaniga, MIT Press, 37-50.
Hutsler, J.J. and L.M. Chalupa. 1994. Neuropeptide Y immunoreactivity identifies a regularly arrayed group of amacrine cells within the cat retina. Journal of Comparative Neurology 346:481-489.
Meissirel, C. and L.M. Chalupa. 1994. Organization of pioneer retinal axons within the optic tract of the rhesus monkey. Proceedings of the National Academy of Science USA 91:3906-3910.
Miguel-Hidalgo, J.J., C.J. Snider, K.J. Angelides and L. M. Chalupa. 1994. Voltage-dependent sodium channel alpha subunit immunoreactivity is expressed by distinct cell types of cat and monkey retina. Visual Neuroscience 11:219-228.
Hutsler, J.J., C.A. White and L.M. Chalupa. 1993. Neuropeptide Y immunoreactivity identifies a group of gamma-type retinal ganglion cells in the cat. Journal of Comparative Neurology 346:481-489.
Skaliora, I., R.P. Scobey and L.M. Chalupa. 1993. Prenatal development of excitability in cat retinal ganglion cells: Action potentials and sodium currents. Journal of Neuroscience 13, 313-323.
Chalulpa, L.M., I. Skaliora and R.P. Scobey. 1993. Responses of isolated cat retinal ganglion cells to injected currents during development. Progress in Brain Research: The Visually Responsive Neuron- From Basic Neurophysiology to Behavior (S. Molotchnikoff and T. P. Hicks, Eds) Elsvier Science Publishers 95:25-31.