Robert Miller, MD

Professor Emeritus, Department of Neuroscience

Professor Emeritus, Department of Neuroscience


Research

Research Summary/Interests

Physiology and Neuroscience of Vision

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. More recently this project has morphed into how D-serine serves to regulate NMDA receptor sensitivity among amacrine and ganglion cells. Second, I have a long-standing interest in the relationships between structure and function of single cells and this has 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. We have recently acquired a two-photon microscope and have initiated new experiments related to events such as back-propagated action potentials in retinal ganglion cells.

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, 3D image reconstruction techniques. The two-photon confocal microscope has now been added to our experimental repertoire and will be focused on the physiological properties of ganglion cell 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.

Publications

Lockridge, AD, Baumann, DC, Akhaphong, B, Abrenica, A, Miller, RF & Alejandro, EU 2016, ‘Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis’ Islets, vol. 8, no. 6, pp. 195-206. https://doi.org/10.1080/19382014.2016.1260797

Gustafson, EG, Stevens, ES & Miller, RF 2015, ‘Dynamic regulation of D-serine release in the vertebrate retina’ J Physiol, vol. 593, no. 4, pp. 843-56. https://doi.org/10.1113/jphysiol.2014.283432

Romero, GE, Lockridge, AD, Morgans, CW, Bandyopadhyay, D & Miller, RF 2014, ‘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, vol. 5, no. 9, pp. 848-54. https://doi.org/10.1021/cn5000106

Gustafson, EC, Morgans, CW, Tekmen, M, Sullivan, SJ, Esguerra, M, Konno, R & Miller, RF 2013, ‘Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase’ J Neurophysiol vol. 110, no. 12, pp. 2718-26. https://doi.org/10.1152/jn.00310.2013

Sullivan, SJ & Miller, RF 2012, ‘AMPA receptor-dependent, light-evoked D-serine release acts on retinal ganglion cell NMDA receptors’ J Neurophysiol, vol. 108, no. 4, pp. 1044-51. https://doi.org/10.1152/jn.00264.2012

Sullivan, SJ, Esguerra, M, Wickham, RJ, Romero, GE, Coyle, JT & Miller, RF 2011, ‘Serine racemase deletion abolishes light-evoked NMDA receptor currents in retinal ganglion cells’ J Physiol, vol. 589, Pt 24, pp. 5997-6006. https://doi.org/10.1113/jphysiol.2011.217059

Sullivan, SJ & Miller, RF 2010, ‘AMPA receptor mediated D-serine release from retinal glial cells’ J Neurochem, vol. 115, no. 6, pp. 1681-9. https://doi.org/10.1111/j.1471-4159.2010.07077.x

Stevens, ER, Gustafson, EC & Miller, RF 2010, ‘Glycine transport accounts for the differential role of glycine vs. D-serine at NMDA receptor coagonist sites in the salamander retina’ Eur J Neurosci, vol. 31, no. 5, pp. 808-16. https://doi.org/10.1111/j.1460-9568.2010.07135.x

Stevens, ER, Gustafson, EC, Sullivan, SJ, Esguerra, M & Miller, RF 2010, ‘Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina’ Neuroreport, vol. 21, no. 4, pp. 239-44. https://doi.org/10.1097/WNR.0b013e32833313b7

Reed, BT, Sullivan, SJ, Tsai, G, Coyle, JT, Esguerra, M & Miller, RF 2009, ‘The glycine transporter GlyT1 controls N-methyl-D-aspartic acid receptor coagonist occupancy in the mouse retina’ Eur J Neurosci, vol. 30, no. 12, pp. 2308-17. https://doi.org/10.1111/j.1460-9568.2009.07020.x

Teaching

Courses

NSC 5540: Biomedical Neuroscience (Summer semester)