This application proposes to study mechanisms of synaptic integration by cholinergic (starburst) amacrine and direction-selective ganglion cells (DSGCs) in the mature rabbit retina with an overall goal to elucidate synaptic and cellular mechanisms underlying complex visual processing in the inner mammalian retina, particularly the detection of motion direction. The proposed studies are based on recent findings of several labs, including ours, that strongly suggest a critical role of starburst cells in the generation of direction selectivity (DS). These studies moved the key unknown issues regarding DS mechanisms to sites upstream of DSGCs and raised some fundamental questions that require a new level experimentation to answer. Here we identify 3 specific aims that will test 2 central hypotheses about the mechanisms underlying the synaptic, cellular, and network functions of starburst cells: 1) to determine the mechanisms of synaptic interaction among starburst cells, 2) to determine the synaptic mechanism of direction-selective light responses in starburst distal processes, 3) to determine the mechanisms of synaptic interaction between starburst and ganglion cells. We will use a powerful wholemount rabbit retinal preparation, which allows the integration of dual patch-clamp recording from starburst cells and DS ganglion cells, simultaneous flash photolysis (UV uncaging) and dual patch clamp, and simultaneous calcium imaging, patch clamp, and light stimulation. The ability to apply these cutting-edge techniques to a living mammalian retina will enable us to gather critical information previously unattainable in other experimental settings. Our experimental approach is unique in that it will directly and systematically measure synaptic interactions among key components of the DS circuit and it will use detailed synaptic physiology to explain the light response properties recorded from the same identified neurons.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY017353-06
Application #
7898785
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
2006-05-05
Project End
2012-07-31
Budget Start
2010-08-01
Budget End
2012-07-31
Support Year
6
Fiscal Year
2010
Total Cost
$392,068
Indirect Cost
Name
Yale University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Chen, Minggang; Lee, Seunghoon; Zhou, Z Jimmy (2017) Local synaptic integration enables ON-OFF asymmetric and layer-specific visual information processing in vGluT3 amacrine cell dendrites. Proc Natl Acad Sci U S A 114:11518-11523
Lee, Seunghoon; Zhang, Yi; Chen, Minggang et al. (2016) Segregated Glycine-Glutamate Co-transmission from vGluT3 Amacrine Cells to Contrast-Suppressed and Contrast-Enhanced Retinal Circuits. Neuron 90:27-34
Xu, Hong-Ping; Burbridge, Timothy J; Ye, Meijun et al. (2016) Retinal Wave Patterns Are Governed by Mutual Excitation among Starburst Amacrine Cells and Drive the Refinement and Maintenance of Visual Circuits. J Neurosci 36:3871-86
Zhou, Elton K; Xu, Hong-Ping (2015) GABAergic regulation of spontaneous spike patterns in the developing rabbit retina. Neurosci Lett 600:137-42
Kuenzel, Wayne J; Kang, Seong W; Zhou, Z Jimmy (2015) Exploring avian deep-brain photoreceptors and their role in activating the neuroendocrine regulation of gonadal development. Poult Sci 94:786-98
Burbridge, Timothy J; Xu, Hong-Ping; Ackman, James B et al. (2014) Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors. Neuron 84:1049-64
Chen, Minggang; Lee, Seunghoon; Park, Silvia J H et al. (2014) Receptive field properties of bipolar cell axon terminals in direction-selective sublaminas of the mouse retina. J Neurophysiol 112:1950-62
Hafler, Brian P; Klein, Zoe A; Jimmy Zhou, Z et al. (2014) Progressive retinal degeneration and accumulation of autofluorescent lipopigments in Progranulin deficient mice. Brain Res 1588:168-74
Lee, Seunghoon; Chen, Lujing; Chen, Minggang et al. (2014) An unconventional glutamatergic circuit in the retina formed by vGluT3 amacrine cells. Neuron 84:708-15
Ackman, James B; Burbridge, Timothy J; Crair, Michael C (2012) Retinal waves coordinate patterned activity throughout the developing visual system. Nature 490:219-25

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