The retina is a well-organized sensory structure with two main pathways of information transfer. In the vertical pathway photoreceptors sense light and transmit Information to bipolar cells, which relay Information to ganglion cells, the output ofthe retina to the brain. Lateral Inhibitory pathways, mediated by horizontal cells in the outer retina and amacrlne cells in the inner retina, modulate this vertical pathway. Inhibition in the inner retina plays several important roles in retinal signal processing, as it both comprises part ofthe center-surround receptive field spatial organization of the retina and affects the gain and temporal processing of retinal signaling. Inhibitory inputs come from two distinct amacrlne cell sources: GABAergic and glycinerglc amacrlne cells, and are mediated by three different inhibitory receptors: GABAC, GABAA and glycine receptors. Previous work has suggested that the distributions and kinetics of these inhibitory receptors are important for determining the properties of light-evoked inhibition in the retina. However, little is known about how the neurotransmitter release properties or spatial activation of amacrine cells that provide inhibitory inputs contribute to bipolar cell inhibition. I will investigate how distinct neurotransmitter release properties in glycinergic and GABAergic amacrine cells temporally shape inhibition in the retina. Additionally, I will determine if GABAergic and glycinergic amacrine cells, which have distinct spatial extents within the retina, create spatially discrete bipolar cell inhibition. These experiments will determine how the connectivity, release and spatial properties of amacrine cells combine to create the total inhibition in the retina. This will add important knowledge to our understanding of the roles of inhibition in retinal signaling. Additionally, as the retina is an accessible neuronal circuit that can be stimulated physiologically, with light, these experiments will add to our knowledge about how multiple inhibitory inputs contribute to total inhibition in the nervous system.

Public Health Relevance

General Statement: To develop approaches to restore normal vision after disease and injury damage the retina, we must first understand how the healthy retina processes visual information. In the proposed research, I will investigate how the properties of modulatory neurons in the retina shape visual signals before they are transmitted to the brain.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Transition Award (R00)
Project #
5R00EY018131-04
Application #
7766219
Study Section
Special Emphasis Panel (NSS)
Program Officer
Greenwell, Thomas
Project Start
2008-02-01
Project End
2012-01-31
Budget Start
2010-02-01
Budget End
2011-01-31
Support Year
4
Fiscal Year
2010
Total Cost
$246,200
Indirect Cost
Name
University of Arizona
Department
Physiology
Type
Schools of Medicine
DUNS #
806345617
City
Tucson
State
AZ
Country
United States
Zip Code
85721
Mazade, Reece E; Eggers, Erika D (2016) Light adaptation alters inner retinal inhibition to shape OFF retinal pathway signaling. J Neurophysiol 115:2761-78
Moore-Dotson, Johnnie M; Klein, Justin S; Mazade, Reece E et al. (2015) Different types of retinal inhibition have distinct neurotransmitter release properties. J Neurophysiol 113:2078-90
Eggers, Erika D; Mazade, Reece E; Klein, Justin S (2013) Inhibition to retinal rod bipolar cells is regulated by light levels. J Neurophysiol 110:153-61
Eggers, Erika D; Klein, Justin S; Moore-Dotson, Johnnie M (2013) Slow changes in Ca2(+) cause prolonged release from GABAergic retinal amacrine cells. J Neurophysiol 110:709-19
Mazade, Reece E; Eggers, Erika D (2013) Light adaptation alters the source of inhibition to the mouse retinal OFF pathway. J Neurophysiol 110:2113-28
Eggers, Erika D; Lukasiewicz, Peter D (2011) Multiple pathways of inhibition shape bipolar cell responses in the retina. Vis Neurosci 28:95-108
Herrmann, Rolf; Heflin, Stephanie J; Hammond, Timothy et al. (2011) Rod vision is controlled by dopamine-dependent sensitization of rod bipolar cells by GABA. Neuron 72:101-10
Sagdullaev, Botir T; Eggers, Erika D; Purgert, Robert et al. (2011) Nonlinear interactions between excitatory and inhibitory retinal synapses control visual output. J Neurosci 31:15102-12
Eggers, Erika D; Lukasiewicz, Peter D (2010) Interneuron circuits tune inhibition in retinal bipolar cells. J Neurophysiol 103:25-37