This research grant proposes to continue the study of the physiology and pharmacology of synapses mediating the center-surround receptive field organization of retinal bipolar cells. Although the broad outline of synaptic interactions and the putative neurotransmitters in the retina are known, detailed cellular and molecular mechanisms underlying signal transfer in bipolar cell synapses are fragmentary, partially because of the technical difficulties associated with stable intracellular recordings from bipolar cells, and partially because of the complexity of the synaptic transfer characteristics and postsynaptic receptors in bipolar cells. This research plan proposes to overcome these difficulties by using the living retinal slices which provide the advantages of both the whole retina and the isolated cell preparations: retinal slices are intact enough so that most synapses are functional and excitable by presynaptic current or by light; and cells in slices are accessible enough so that multi-electrode recordings can be performed under visual control. Moreover, this research will also take advantage of the newly available specific glutamate and GABA receptor analogues to characterize the postsynaptic receptor subtypes mediating the light responses of bipolar cells. Synapses mediating the central and lateral inputs of bipolar cells will be individually studied when they are activated by light, presynaptic current injection or by application of neurotransmitter analogues. Postsynaptic conductance changes, kinetics and ionic components of postsynaptic currents, input-output relations and voltage gains of the photoreceptor-second-order cell, horizontal cell-cone and horizontal cell-bipolar cell synapses will be determined. Postsynaptic actions of glutamate (putative photoreceptor transmitter) and GABA (putative HC transmitter) and their analogues on bipolar cells, HCs and cones will be examined. Experiments in this proposal are designed to address a set of specific questions which include: (1) What are the postsynaptic actions and the input-output relations of the rod and cone output synapses in bipolar cells and horizontal cells? (2) What glutamate and GABA receptor subtypes are present and what function do they serve in bipolar cells and horizontal cells? (3) Is the bipolar cell surround response mediated by the feedback or the forward synapse? The long term goal of this project is to integrate results obtained into a complete and detailed description of how individual synapses are responsible for organizing the center-surround receptive fields of bipolar cells - an ubiquitous functional unit across species and the fundamental code for spatial resolution in the visual system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY004446-11
Application #
3258878
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1982-02-01
Project End
1995-09-29
Budget Start
1992-09-30
Budget End
1993-09-29
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Baylor College of Medicine
Department
Type
Schools of Medicine
DUNS #
074615394
City
Houston
State
TX
Country
United States
Zip Code
77030
Pang, Ji-Jie; Yang, Zhuo; Jacoby, Roy A et al. (2018) Cone synapses in mammalian retinal rod bipolar cells. J Comp Neurol 526:1896-1909
Cowan, Cameron S; Sabharwal, Jasdeep; Seilheimer, Robert L et al. (2017) Distinct subcomponents of mouse retinal ganglion cell receptive fields are differentially altered by light adaptation. Vision Res 131:96-105
Tse, Dennis Y; Kim, Seong Jae; Chung, Inyoung et al. (2017) The ocular toxicity and pharmacokinetics of simvastatin following intravitreal injection in mice. Int J Ophthalmol 10:1361-1369
He, Feng; Agosto, Melina A; Anastassov, Ivan A et al. (2016) Phosphatidylinositol-3-phosphate is light-regulated and essential for survival in retinal rods. Sci Rep 6:26978
Wang, Jing; Jacoby, Roy; Wu, Samuel M (2016) Physiological and morphological characterization of ganglion cells in the salamander retina. Vision Res 119:60-72
Cowan, Cameron S; Abd-El-Barr, Muhammad; van der Heijden, Meike et al. (2016) Connexin 36 and rod bipolar cell independent rod pathways drive retinal ganglion cells and optokinetic reflexes. Vision Res 119:99-109
Eblimit, Aiden; Nguyen, Thanh-Minh T; Chen, Yiyun et al. (2015) Spata7 is a retinal ciliopathy gene critical for correct RPGRIP1 localization and protein trafficking in the retina. Hum Mol Genet 24:1584-601
Khan, A Kareem; Tse, Dennis Y; van der Heijden, Meike E et al. (2015) Prolonged elevation of intraocular pressure results in retinal ganglion cell loss and abnormal retinal function in mice. Exp Eye Res 130:29-37
Kim, Jin Young; Song, Ji Yun; Karnam, Santi et al. (2015) Common and distinctive localization patterns of Crumbs polarity complex proteins in the mammalian eye. Gene Expr Patterns 17:31-7
Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E et al. (2015) The Effect of PKC? on the Light Response of Rod Bipolar Cells in the Mouse Retina. Invest Ophthalmol Vis Sci 56:4961-74

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