Intrinsically photosensitive retinal ganglion cells: diversity of form and function
Associate Professor, Department of Neurobiology, Northwestern University
Assistant Professor, Department of Neurobiology, Northwestern University
Undergraduate Institution and Major/Degree:
Luther College, Decorah, IA
Bachelor of Arts: Biology and Honors Psychology 2006
Paulo Kofuji, Ph.D.
In mammals, photic information is exclusively processed by the retina and reaches the brain through the optic nerve. The eyes are equipped with at least two functionally and anatomically distinct light-detecting systems, the classic image-forming system involving rods and cones and a non-image forming, irradiance detection system. The non–image-forming photoreceptive system entrains the circadian timing system and regulates pineal melatonin secretion and pupillary constriction. A small subpopulation of ganglion cells in the retina express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). These ipRGCs project to several brain areas involved in non-image forming vision including the suprachiasmatic nuclei of the hypothalamus (SCN), which drive the mammalian circadian rhythm, as well as the olivary pretectal nuclei (OPN), which control the pupillary light reflex. These cells are now thought to be the sole pathway through which non-image forming visual responses are conveyed to both the SCN and OPN. In addition to their intrinsic ability to respond directly to light, emerging evidence now indicates that likely all ipRGCs receive synaptic information relayed from rod/cone photoreceptors.
Thus, the central question of my thesis research is: How do ipRGCs integrate intrinsic (melanopsin-based) and extrinsic (synaptic) inputs to signal light information to the brain? Specifically, I am examining the diversity that exists within the ipRGC population utilizing a mouse model developed in our lab in which ipRGCs are labeled in vivo with EGFP. This mouse model allows us to identify and target single ipRGCs in the isolated retina and places us in a unique position to study the physiology and morphology of ipRGCs at the single cell level. Thus far, our research has identified the three morphological subpopulations of ipRGC in our mouse line (Schmidt et al., 2008), identified divergent functional properties across two subpopulations of ipRGC, M1 and M2 cells (Schmidt and Kofuji, 2009), and determined that ipRGCs begin to receive synaptic contacts starting at postnatal day 11 and that likely all ipRGCs receive synaptic inputs from the outer retina by adulthood (Schmidt et al., 2008). Future research will focus on identifying the retinal pathways that have synaptic input to these distinct subpopulations of ipRGC and the functional consequences of such inputs as well as intrinsic differences in these ipRGC subtypes that might underlie their distinct physiological profiles.
- Paul Mermelstein
- Eric Newman
- Paulo Kofuji
Courses Taken Beyond the Core Courses:
- PSY 5031 Perception
- PUBH 6450 Biostatistics I
- PUBH 6451 Biostatistics II
- PHSL 5201 Computational Neuroscience
Graduate Level Minor:
- Supporting Program
- Society for Neuroscience Annual Meeting November 2006 , 2007, 2008
- Association for Research in Vision and Ophthalmology 2009, 2010
- European Retina Meeting, Oldenburg , Germany 2009
- International Society for Eye Research Biennial Meeting, Montreal , Canada 2010
- Eric Newman (chair)
- Robert Miller
- Dwight Burkhardt
- Paulo Kofuji (advisor)
- Chew KS, Schmidt TM, Rupp AC, Kofuji P, Trimarchi JM. Loss of gq/11 genes does not abolish melanopsin phototransduction. PLoS One. 2014 May 28;9(5):e98356.
- Schmidt TM, Alam NM, Chen S, Kofuji P, Li W, Prusky GT, Hattar S. A role for melanopsin in alpha retinal ganglion cells and contrast detection. Neuron. 2014 May 21;82(4):781-788.
- Sand AM, Schmidt TM, Kofuji P. Diverse types of ganglion cell photoreceptors in the mammalian retina. Prog Retin Eye Res. 2012;31(4):287-302.
- Schmidt TM†, Chen S-K, Hattar S.†Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci. 2011;34 (11):572-580.
- Schmidt TM, Do MT, Dacey DM, Lucas R, Hattar S, Matynia A. Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. J Neurosci. 2011;31(45): 16094-101.
- Schmidt TM, Kofuji P. An isolated retinal preparation to record light responses from genetically labeled retinal ganglion cells. J Vis Exp. 2011 Jan 26;(47). pii: 2367.
- Perez-Leighton CE*, Schmidt TM*, Abramovitz J, Birnbaumer L, Kofuji P. Intrinsic phototransduction persists in melanopsin-expressing ganglion cells lacking diacylglycerol-sensitive TRPC channel subunits. Eur J Neurosci. 2011;33(5):856-867.
- Schmidt TM, Kofuji P. Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse. J Comp Neurol. 2011;519(8):1492-504.
- Tang X, Schmidt TM, Perez-Leighton CE, Kofuji P. Inwardly rectifying potassium channel Kir4.1 is responsible for the native inward potassium conductance of satellite glia cells in sensory ganglia. Neuroscience 2010;166(2):397-407.
- Schmidt TM, Kofuji P. Differential cone pathway influence on intrinsically photosensitive retinal ganglion cell subtypes. J Neurosci. 2010;30(48):16262-16271.
- Schmidt TM. Role of melastatin-related transient receptor potential channel TRPM1 in the retina: Clues from horses and mice. J Neurosci. 2009;29(38):11720-11722.
- Schmidt TM, Kofuji P. Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J Neurosci. 2009;29(2): 476-482.
- Schmidt TM, Kofuji P. Novel insights into non-image forming visual processing in the retina. Cellscience. 2008;5(1):77-83.
- Schmidt TM, Taniguchi K, Kofuji P. Intrinsic and extrinsic light responses in melanopsin-expressing ganglion cells during mouse development. J Neurophysiol. 2008 Jul;100(1):371-84.
Awards and Honors:
- McElroy Trust Fellowship for Undergraduate Research, 2005
- University of Minnesota Graduate School Fellowship, 2006-2008
- Morris Smithberg Memorial Prize, Graduate Program in Neuroscience, University of Minnesota , 2007
- Milne/Brandenburg Endowment Prize for Student Achievement, Graduate Program in Neuroscience, University of Minnesota , 2009
- Stark Award for Travel, Graduate Program in Neuroscience, University of Minnesota , 2009
- Milne and Brandenburg Research Award for Exceptional Graduate Research in the Biomedical Sciences, Mayo Medical Foundation, University of Minnesota , 2010
- Association for Research in Vision and Ophthalmology Travel Grant, 2010
- International Society for Eye Research Travel Grant, 2010
- Society for Neuroscience (2007-present)
- American Physiological Society (2008-2009)
- Association for Research in Vision and Ophthalmology (2008-present)
- International Society for Eye Research (2010)
- Rochester, MN