The long term objective of this project is to determine the functions of glial cells (Muller cells and astrocytes) in the mammalian retina. Preliminary studies from our laboratory show that light-evoked neuronal activity can induce calcium increases in retinal gila and that activation of glial cells can either facilitate or depress synaptic transmission onto ganglion cells.
The specific aims for the project period are: 1) Identify the mechanisms by which light-evoked neuronal activity elicits calcium increases in retinal glial cells. Hypotheses to be tested include: i) neurotransmitters released from synaptic terminals evoke glial calcium increases, ii) transmitters released from extra-synaptic regions of ganglion cells evoke glial calcium increases. 2) Determine the cellular mechanism by which glial cells hyperpolarize retinal ganglion cells. We will test the hypothesis that glial cells inhibit ganglion cells by opening ganglion cell G-protein coupled inwardly rectifying K+ channels (GIRKs). 3) Identify the mechanisms by which glial cells facilitate synaptic transmission. Hypotheses to be tested include: Gila facilitate synaptic transmission i) by releasing ATP and activating presynaptic P2X, P2Y or A2 receptors, ii) by releasing glutamate and activating presynaptic mGluRs, iii) by releasing D-serine and facilitating postsynaptic NMDA receptors. 4) Identify the mechanisms by which glial cells depress synaptic transmission. Hypotheses to be tested include: Gila depress synaptic transmission i) by releasing ATP and activating presynaptic A1 receptors, ii) by releasing glutamate and activating presynaptic mGluRs, iii) by releasing glutamate and desensitizing postsynaptic GluRs. Glial cells have been implicated in many types of retinal pathology, including diabetic retinopathy, glaucoma and macular degeneration. Knowledge of the basic physiological properties of retinal gila and their interactions with neurons will add to our understanding of how these cells contribute to retinal pathology. The research outlined in this proposal will provide significant progress towards this goal.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY004077-28S1
Application #
8005880
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
1990-07-01
Project End
2011-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
28
Fiscal Year
2010
Total Cost
$215,751
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Neurosciences
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Nippert, Amy R; Biesecker, Kyle R; Newman, Eric A (2018) Mechanisms Mediating Functional Hyperemia in the Brain. Neuroscientist 24:73-83
Srienc, Anja I; Biesecker, Kyle R; Shimoda, Angela M et al. (2016) Ischemia-induced spreading depolarization in the retina. J Cereb Blood Flow Metab 36:1579-91
Biesecker, Kyle R; Srienc, Anja I; Shimoda, Angela M et al. (2016) Glial Cell Calcium Signaling Mediates Capillary Regulation of Blood Flow in the Retina. J Neurosci 36:9435-45
Kornfield, Tess E; Newman, Eric A (2015) Measurement of Retinal Blood Flow Using Fluorescently Labeled Red Blood Cells. eNeuro 2:
Newman, Eric A (2015) Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters. Philos Trans R Soc Lond B Biol Sci 370:
MacVicar, Brian A; Newman, Eric A (2015) Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol 7:
Kur, Joanna; Newman, Eric A (2014) Purinergic control of vascular tone in the retina. J Physiol 592:491-504
Kornfield, Tess E; Newman, Eric A (2014) Regulation of blood flow in the retinal trilaminar vascular network. J Neurosci 34:11504-13
Newman, Eric A (2013) Functional hyperemia and mechanisms of neurovascular coupling in the retinal vasculature. J Cereb Blood Flow Metab 33:1685-95
Kur, Joanna; Newman, Eric A; Chan-Ling, Tailoi (2012) Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Prog Retin Eye Res 31:377-406

Showing the most recent 10 out of 56 publications