This research proposal is an experimenal investigation into (1) the identification of synaptic transmitters, (2) the physiological basis of transmitter action at the single cell level, and (3) the morphological identification of physiologically and pharmacologically characterized cells. Inhibitory and excitatory transmitter agonists and antagonists are added to the bathing medium using perfused-retina eyecup preparations of rabbits and several types of amphibians (mudpuppy and tiger salamander). Analysis of drug action is based on intracellular electrode experiments using conventional recording techniques, single electrode voltage clamp techniques ad a lock-in amplifier for quantitative measurements of conductance changes. A similar, parallel set of experiments will be carried out using enzyme dissociated cells maintained in tissue culture conditions. Intracellular recording of single dissociated cells will be analyzed as agonists/antagonists are added to the bathing medium, iontophoretically applied, or introduced through pressure injection. The isolated retina of amphibians and rabbits will be studied for types and levels of amino acids released into the bathing medium, using reverse-phase high performance liquid chromatography. Particular emphasis will be placed on the identity of rod and cone transmitters. These experiments will also be combined with tissue culture techniques to fractionate the retina into limited neuronal populations, through the use of neuroactive ligands. The goal of this research is to identify synaptic transmitters and associate them with specific pathways and cell types. Several disease states which afflict the retina (retinitis pigmentosa; macular degeneration), show prolonged states in which photoreceptor function is compromised while leaving a more or less intact retina. An understanding of the chemicals involved in photoreceptor transmission, together with the synaptic receptors which mediate their action may help in the design of drug therapy to assist patients with limited vision.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY003014-12
Application #
3257336
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1988-03-01
Project End
1989-02-28
Budget Start
1988-07-01
Budget End
1989-02-28
Support Year
12
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Gustafson, Eric G; Stevens, Eric S; Miller, Robert F (2015) Dynamic regulation of D-serine release in the vertebrate retina. J Physiol 593:843-56
Romero, Gabriel E; Lockridge, Amber D; Morgans, Catherine W et al. (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 5:848-54
Gustafson, Eric C; Morgans, Catherine W; Tekmen, Merve et al. (2013) Retinal NMDA receptor function and expression are altered in a mouse lacking D-amino acid oxidase. J Neurophysiol 110:2718-26
Sullivan, Steve J; Miller, Robert F (2012) AMPA receptor-dependent, light-evoked D-serine release acts on retinal ganglion cell NMDA receptors. J Neurophysiol 108:1044-51
Sullivan, Steve J; Miller, Robert F (2010) AMPA receptor mediated D-serine release from retinal glial cells. J Neurochem 115:1681-9
Stevens, Eric R; Gustafson, Eric C; Miller, Robert F (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 31:808-16
Stevens, Eric R; Gustafson, Eric C; Sullivan, Steven J et al. (2010) Light-evoked NMDA receptor-mediated currents are reduced by blocking D-serine synthesis in the salamander retina. Neuroreport 21:239-44
Reed, Brian T; Sullivan, Steven J; Tsai, Guochuan et al. (2009) The glycine transporter GlyT1 controls N-methyl-D-aspartic acid receptor coagonist occupancy in the mouse retina. Eur J Neurosci 30:2308-17
Perge, János A; Koch, Kristin; Miller, Robert et al. (2009) How the optic nerve allocates space, energy capacity, and information. J Neurosci 29:7917-28
Balasubramanian, Vijay; Sterling, Peter (2009) Receptive fields and functional architecture in the retina. J Physiol 587:2753-67

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