This application proposes to continue our ongoing studies of the mechanisms of spontaneous rhythmic activity and the establishment of functional synaptic circuits in the developing mammalian retina. It will test two hypotheses: (1) the spontaneous waves that appear during two different developmental stages (conventional and ribbon synaptogenesis in the inner retina) are produced by different networks of intrinsic oscillators;(2) the complex, asymmetric synaptic circuitry involving starburst cells is established by a process of coordinated reorganization and refinement of synaptic connectivity and synaptic function. To test these hypotheses, we propose to integrate several cutting-edge electrophysiological techniques, which will enable the direct measurement of synaptic function and synaptic connectivity in an anatomically well-defined and functionally well-specified network at various developmental stages. The proposed studies will pursue three specific aims: (1) to determine the cellular mechanisms underlying spontaneous retinal waves, (2) to determine the mechanism and function of synaptic interaction during synaptogenesis.and retinal waves, (3) to understand the development of starburst synaptic function and circuitry. Results from these studies will allow the integration of functional and anatomical information about the developing retina in a way previously unattainable in other experimental settings and may lead to better understanding of visual system development in health and diseases.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
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Yale University
Schools of Medicine
New Haven
United States
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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
Xu, Hong-ping; Furman, Moran; Mineur, Yann S et al. (2011) An instructive role for patterned spontaneous retinal activity in mouse visual map development. Neuron 70:1115-27
Lee, Seunghoon; Kim, Kyongmin; Zhou, Z Jimmy (2010) Role of ACh-GABA cotransmission in detecting image motion and motion direction. Neuron 68:1159-72
Zhou, Z Jimmy; Lee, Seunghoon (2008) Synaptic physiology of direction selectivity in the retina. J Physiol 586:4371-6
Zheng, Jijian; Lee, Seunghoon; Zhou, Z Jimmy (2006) A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves. Nat Neurosci 9:363-71
Lee, Seunghoon; Zhou, Z Jimmy (2006) The synaptic mechanism of direction selectivity in distal processes of starburst amacrine cells. Neuron 51:787-99
Zheng, Ji-Jian; Lee, Seunghoon; Zhou, Z Jimmy (2004) A developmental switch in the excitability and function of the starburst network in the mammalian retina. Neuron 44:851-64
Casini, G; Dal Monte, M; Fornai, F et al. (2004) Neurokinin 1 receptor expression and substance P physiological actions are developmentally regulated in the rabbit retina. Neuroscience 124:147-60
Syed, Mohsin Md; Lee, Seunghoon; Zheng, Jijian et al. (2004) Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina. J Physiol 560:533-49
Zhou, Z J (2001) The function of the cholinergic system in the developing mammalian retina. Prog Brain Res 131:599-613

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