Intrinsically photosensitive retinal ganglion cells: diversity of form and function
Assistant Professor, Department of Neurobiology, Northwestern University
Undergraduate Institution and Major/Degree:
Luther College, Decorah, IA
Bachelor of Arts: Biology and Honors Psychology 2006
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)
- Sand AM, Schmidt TM, Kofuji P (2012) Diverse types of ganglion cell photoreceptors in the mammalian retina. Progress in Retinal and Eye Research, in press.
- Schmidt TM and Kofuji P (2011) An isolated retinal preparation to record light responses from genetically labeled retinal ganglion cells. J Vis Exp 47.
- Perez-Leighton CE*, Schmidt TM*, Abramovitz J, Birnbaumer L, Kofuji P (2011) Intrinsic phototransduction persists in melanopsin-expressing ganglion cells lacking diacylglycerol-sensitive TRPC channel subunits. Eur J Neurosci 33(5):856-867.
- Schmidt TM and Kofuji P (2011) Form and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse. J Comp Neurol 519(8): 1492-1504.
- Schmidt TM†, Chen S-K, Hattar S† (2011) Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci 34 (11): 572-580.
- Schmidt TM, Do MT, Dacey DM, Lucas R, Hattar S, Matynia A (2011) Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function. J Neurosci 31(45): 16094-101.
- Tang X, Schmidt TM, Perez-Leighton CE, Kofuji P (2010) Inwardly rectifying potassium channel Kir4.1 is responsible for the native inward potassium conductance of satellite glia cells in sensory ganglia. Neuroscience 166(2): 397-407.
- Schmidt TM and Kofuji P (2010) Differential cone pathway influence on intrinsically photosensitive retinal ganglion cell subtypes. J Neurosci 30 (48): 16262-16271.
- Schmidt TM and Kofuji P (2009) Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J Neurosci 29(2): 476-482.
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