We propose to study visual signalling in the mammalian retina. One group of experiments will focus on visual transduction, while a second will focus on the neural circuits over which transduced signals flow to the retinal ganglion cells. The experiments on visual transduction will examine the still poorly- understood processes that terminate the response to light. By making electrical recordings from transgenic mouse rods as well as normal primate photoreceptors we will ask: 1. Must rhodopsin be phosphorylated in the C terminal region for its catalytic activity to shut off normally in vivo? When does phosphorylation occur? Is phosphorylation at a single site sufficient to elicit complete shutoff? 2. Must arrestin bind to phosphorylated rhodopsin to complete shut-off? When does arrestin bind? How much does phosphorylation alone reduce catalytic activity? 3. Does the Ca-binding protein recoverin, which regulates rhodopsin shutoff, make the single photon response reproducible, mediate the gain reduction that occurs in background light, or both? 4. What molecular defect in rhodopsin is responsible for the anomalously- prolonged single photon responses that occur in normal primate rods? Is older rhodopsin more likely to be defective? 5. What are the dynamics of intracellular Ca in primate cones, and how do they relate to the diphasic waveform of the cone flash response? The experiments on neural circuitry will use a multielectrode array to record from ganglion cells in isolated primate retinas. We will ask: 6. How do the receptive fields of populations of ganglion cells sample visual images? 7. Do ganglion cells in the primate retina undergo concerted firing or do they only signal independently? If concerted firing is present, what cells are involved, over what length scale are signals correlated, and how does concerted firing contribute to the detection of contrast and color? 8. What is the contribution to ganglion cell receptive fields of electrical coupling between photoreceptors and horizontal cell feedback on photoreceptors? 9. Are the cones themselves the dominant site of chromatic adaptation in the retina, or are downstream cells involved? Can adaptation of one cone class change the gain of signals from another cone class?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005750-15
Application #
2888181
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1985-04-01
Project End
2001-12-31
Budget Start
1999-04-01
Budget End
2001-12-31
Support Year
15
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Stanford University
Department
Biology
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Burns, Marie E; Mendez, Ana; Chen, Ching-Kang et al. (2006) Deactivation of phosphorylated and nonphosphorylated rhodopsin by arrestin splice variants. J Neurosci 26:1036-44
Makino, Clint L; Dodd, R L; Chen, J et al. (2004) Recoverin regulates light-dependent phosphodiesterase activity in retinal rods. J Gen Physiol 123:729-41
Burns, Marie E; Mendez, Ana; Chen, Jeannie et al. (2002) Dynamics of cyclic GMP synthesis in retinal rods. Neuron 36:81-91
Mendez, A; Burns, M E; Sokal, I et al. (2001) Role of guanylate cyclase-activating proteins (GCAPs) in setting the flash sensitivity of rod photoreceptors. Proc Natl Acad Sci U S A 98:9948-53
Baylor, D A; Burns, M E (1998) Control of rhodopsin activity in vision. Eye (Lond) 12 ( Pt 3b):521-5
Sung, C H; Makino, C; Baylor, D et al. (1994) A rhodopsin gene mutation responsible for autosomal dominant retinitis pigmentosa results in a protein that is defective in localization to the photoreceptor outer segment. J Neurosci 14:5818-33
Raport, C J; Lem, J; Makino, C et al. (1994) Downregulation of cGMP phosphodiesterase induced by expression of GTPase-deficient cone transducin in mouse rod photoreceptors. Invest Ophthalmol Vis Sci 35:2932-47
Meister, M; Pine, J; Baylor, D A (1994) Multi-neuronal signals from the retina: acquisition and analysis. J Neurosci Methods 51:95-106
DeVries, S H; Baylor, D A (1993) Synaptic circuitry of the retina and olfactory bulb. Cell 72 Suppl:139-49
Baylor, D (1992) Transduction in retinal photoreceptor cells. Soc Gen Physiol Ser 47:151-74

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