My primary research interest is focused on the vertebrate retina, a unique, well organized neural network that carries out sophisticated computations on the visual image. Four general areas occupy most of my experimental efforts. The first relates to the mechanisms of synaptic transmission in the retina, with special emphasis on glutamate receptors. Second, I have a long-standing interest in the relationships between structure and function and this had led to computational approaches to these problems, including the use of computer simulations to replicate physiological observations. In recent years my colleagues and I have developed models of multichannel impulse encoding, the role of T-type calcium channels in dendritic integration and impulse generation and the role of NMDA and AMPA receptors in synaptic transmission. A third area involves the use of fluorescent dyes to study functional properties of cells, including the use of activity-dependent dyes, combined with confocal microscopy and dyes to study intracellular calcium, pH, and chloride activity. A fourth research area relates to the function of glial cells in the retina, principally the Müller cells and how they generate calcium waves and respond to externally applied NAD.
Methods used in my laboratory include intracellular, whole-cell and patch-electrode electrophysiological techniques applied to the intact retina, retinal slices, and dissociated cells. Optical techniques include fluorescence microscopy, confocal microscopy, and 3D image reconstruction techniques. We are adding two-photon, confocal microscopy to combine this with electrophysiology for analyzing intricate properties of dendrites. We also use high-speed computers with specialized software (Neuron and MCell) to carry out studies of single cell structure and function relationships, including diffusion of neurotransmitter and receptor kinetics.
Boycott Award for research (2002)
2008 Proctor Medal Award from the Association for Research in Vision and Ophthalmology
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
Gustafson EG, Stevens ES, Miller RF. Dynamic regulation of D-serine release in the vertebrate retina. J Physiol. 2015 Feb 15;593(4):843-56.
Romero GE, Lockridge AD, Morgans CW, Bandyopadhyay D, Miller RF. The postnatal development of D-serine in the retinas of two mouse strains, including a mutant mouse with a deficiency in D-amino acid oxidase and a serine racemase knockout mouse. ACS Chem Neurosci. 2014 Sep 17;5(9):848-54.
Gustafson EC, Morgans CW, Tekmen M, Sullivan SJ, Esguerra M, Konno R, Miller RF. Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase. J Neurophysiol. 2013 Dec;110(12):2718-26.
Sullivan SJ, Miller RF. AMPA receptor-dependent, light-evoked D-serine release acts on retinal ganglion cell NMDA receptors. J Neurophysiol. 2012 Aug;108(4):1044-51.
Sullivan SJ, Esguerra M, Wickham RJ, Romero GE, Coyle JT, Miller RF. Serine racemase deletion abolishes light-evoked NMDA receptor currents in retinal ganglion cells. J Physiol. 2011 Dec 15;589(Pt 24):5997-6006.
Sullivan SJ, Miller RF. AMPA receptor mediated D-serine release from retinal glial cells. J Neurochem. 2010 Dec;115(6):1681-9.
Stevens ER, Gustafson EC, Miller RF. Glycine transport accounts for the differential role of glycine vs. D-serine at NMDA receptor coagonist sites in the salamander retina. Eur J Neurosci. 2010 Mar;31(5):808-16.
Stevens ER, Gustafson EC, Sullivan SJ, Esguerra M, Miller RF. Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina. Neuroreport. 2010 Mar 10;21(4):239-44.
Reed BT, Sullivan SJ, Tsai G, Coyle JT, Esguerra M, Miller RF.The glycine transporter GlyT1 controls N-methyl-D-aspartic acid receptor coagonist occupancy in the mouse retina. Eur J Neurosci. 2009 Dec;30(12):2308-17. Epub 2009 Dec 10.
Miller RF. Cell communication mechanisms in the vertebrate retina the proctor lecture. Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5184-98.
Mitra P, Miller RF. Mechanism underlying rebound excitation in retinal ganglion cells. Vis Neurosci. 2007 Sep-Oct;24(5):709-31.
Royer AS, Miller RF. Dendritic impulse collisions and shifting sites of action potential initiation contract and extend the receptive field of an amacrine cell. Vis Neurosci. 2007 Jul-Aug;24(4):619-34.
Gustafson EC, Stevens ER, Wolosker H, Miller RF. Endogenous D-serine contributes to NMDA-receptor-mediated light-evoked responses in the vertebrate retina. J Neurophysiol. 2007 Jul;98(1):122-30.
Mitra P, Miller RF. Normal and rebound impulse firing in retinal ganglion cells. Vis Neurosci. 2007 Jan-Feb;24(1):79-90.
Henderson D, Miller RF. Low-voltage activated calcium currents in ganglion cells of the tiger salamander retina: experiment and simulation. Vis Neurosci. 2007 Jan-Feb;24(1):37-51.
Miller RF, Staff NP, Velte TJ. Form and function of ON-OFF amacrine cells in the amphibian retina. J Neurophysiol. 2006 May;95(5):3171-90.
Current Graduate Students:
Nathalia Torres Jimenez (Neuroscience, University of Minnesota).
Former Graduate Students:
Steve Sullivan (Ph.D. 2011, Neuroscience, University of Minnesota).
Eric Gustafson (Ph.D. 2009, Neuroscience, University of Minnesota).
Eric Stevens (Ph.D. 2007, Neuroscience, University of Minnesota).
Dori Henderson (Ph.D. 2001, Neuroscience, University of Minnesota).
Toby Velte (Ph.D. 1995, Neuroscience, University of Minnesota).
Weifeng Yu (Ph.D., Physiology, 1994). Postdoctoral Fellow, Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, MD.