Dynamic regulation of the NMDA receptor coagonist D-serine in the mammalian retina: Why the universe prefers L-amino acids but the retina sees things differently
Postdoctoral Fellow, Oregon Health Sciences University
Postdoctoral Research Fellow
University College, London, United Kingdom
Undergraduate Institution and Major/Degree:
Minnesota State University Mankato, BS in Human Biology and Psychology
Robert Miller, M.D.
Ion conductance through the N-methyl D-aspartate receptor (NMDAR) not only contributes to the electrical excitability of neurons, but can also trigger intracellular signaling cascades capable of modifying the properties of neurons and, subsequently, their relative influence on each other. NMDA receptor activation requires the simultaneous binding of glutamate agonist and also a coagonist. Recent evidence suggests that D-serine, synthesized and released by glial cells, serves as the primary NMDAR coagonist in various regions of the nervous system, including the retina. However, little is known about how D-serine is released. Part of my research utilizes a number of biochemical techniques (capillary electrophoresis and enzymatic assays) to measure D-serine and determine how it's released in the retina.
My current work has focused on characterizing the electrical responses of retinal ganglion cells in a mouse lacking serine racemase (SRKO), the only known D-serine synthesizing enzyme. Using whole-cell patch recordings, I found SRKO mice to have dramatically attenuated light-evoked NMDA currents, which can be rescued by the addition of coagonist. This data implies that D-serine is a critical signaling molecule in the retina.
- Bob Miller
- Paul Mermelstein
- David Redish
- Teresa Nick
Courses Taken Beyond the Core Courses:
- PHSL 5201 Computational Neuroscience I
- NSC 5202 Theoretical Neuroscience
- PUBH 6450 Biostatistics I
- CMB 8361 Neuro-Immune Interactions
Conferences Attended and Presentations:
- Society for Neuroscience Annual Meeting: Fall 2005, 2006, 2007
- Assoc for Research in Vision and Ophthalmology Meeting: Spring 2008
- Eric Newman (chair)
- Paulo Kofuji
- Michael Bowser
- 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;110:2718-26.
- Sullivan SJ, Miller RF. AMPA receptor dependent, light-evoked D-serine release acts on retinal ganglion cell NMDA receptors. J Neurophysiol. 2012;108:044-1051.
- Sullivan SJ, Esguerra M, Wickham RJ, Romero GE, Coyle J, Miller RF. Serine racemase deletion abolishes light-evoked NMDA receptor currents in retinal ganglion cells. J Physiol. 2011;24:5997-6006.
- Sullivan SJ, Miller RF. AMPA receptor mediated D-serine release from retinal glial cells. J Neurochem. 2010;115:1681-1689.
- 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. 2009;21:239-244.
- Reed BT, Sullivan SJ, Guochuan T, Coyle J, Esguerra M, Miller RF. The glycine transporter GlyT1 controls NMDA receptor coagonist occupancy in the mouse retina. Eur J Neurosci. 2009;30:2308-2317.
Awards and Honors:
- Fellowship on NIH Training Grant: 2005, 2007
- Society for Neuroscience
- Association for Research in Vision and Ophthalmology
- Eden Prairie , MN