The ability of the dark-adapted visual system to count photon absorptions has been known for many years; however, the biophysical mechanisms which make photon detection and counting possible are not understood. Much of rod vision occurs at light levels where photon absorptions occur rarely; thus, failure of these biophysical processes will severely impair rod vision. The reliability of photon counting means that the transduction process in the rod outer segment must produce distinguishable responses to absorption of O, 1, or 2 photons, and that these signals are reliably transmitted from the rod to the rest of the visual system. Current understanding of signal transduction and synaptic transmission cannot account for this level of performance. Experiments proposed here will determine the mechanisms mediating reliable transduction of single photon absorptions and reliable transmission of these responses to second order cells. Studies of phototransduction will determine how each absorbed photon produces a nearly identical current response. This reproducibility is essential for reliable photon counting, but is surprising given the expected statistical fluctuations in the small number of molecules involved, particularly in the shutoff of photoexcited rhodopsin. Elements of the transduction cascade will be selectively altered to determine if they are necessary for reproducible single photon responses. Studies of synaptic transmission will determine how single photon responses are reliably transmitted to second order cells in the retina, and how pre-synaptic mechanisms separate light signals from photoreceptor noise. The single photon signal traversing the synapse and the noise generated in synaptic transmission will be studied by monitoring the post-synaptic current in a bipolar cell while controlling the rod voltage. Signal transfer to bipolar cells also separates light signals from photoreceptor noise. A likely mechanism mediating this synaptic filtering is the control of the Ca2+ concentration in the synaptic terminal. To test this idea, the kinetics of Ca2+ changes in the terminal will be measured with fluorescent indicators and compared to the kinetics of signal transfer. A further test will be made by determining how the kinetics of signal transfer are altered when the buffering capacity of the terminal is changed.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY011850-01
Application #
2372539
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1997-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Washington
Department
Physiology
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Bleckert, Adam; Zhang, Chi; Turner, Maxwell H et al. (2018) GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells. Proc Natl Acad Sci U S A 115:E12083-E12090
Turner, Maxwell H; Schwartz, Gregory W; Rieke, Fred (2018) Receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina. Elife 7:
Grimes, William N; Baudin, Jacob; Azevedo, Anthony W et al. (2018) Range, routing and kinetics of rod signaling in primate retina. Elife 7:
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Della Santina, Luca; Kuo, Sidney P; Yoshimatsu, Takeshi et al. (2016) Glutamatergic Monopolar Interneurons Provide a Novel Pathway of Excitation in the Mouse Retina. Curr Biol 26:2070-2077
Kuo, Sidney P; Schwartz, Gregory W; Rieke, Fred (2016) Nonlinear Spatiotemporal Integration by Electrical and Chemical Synapses in the Retina. Neuron 90:320-32
Turner, Maxwell H; Rieke, Fred (2016) Synaptic Rectification Controls Nonlinear Spatial Integration of Natural Visual Inputs. Neuron 90:1257-1271
Zylberberg, Joel; Cafaro, Jon; Turner, Maxwell H et al. (2016) Direction-Selective Circuits Shape Noise to Ensure a Precise Population Code. Neuron 89:369-383
Hass, Charles A; Angueyra, Juan M; Lindbloom-Brown, Zachary et al. (2015) Chromatic detection from cone photoreceptors to V1 neurons to behavior in rhesus monkeys. J Vis 15:1
Hoon, Mrinalini; Sinha, Raunak; Okawa, Haruhisa et al. (2015) Neurotransmission plays contrasting roles in the maturation of inhibitory synapses on axons and dendrites of retinal bipolar cells. Proc Natl Acad Sci U S A 112:12840-5

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