Synaptic connections in the nervous system are highly specific. In some regions of the central nervous system, synapse specificity arises from the reorganization of more diffuse, early patterns of connectivity whereas in other regions, precise patterns may be present from the very beginning. Thus, one of the most challenging and important issues in neurobiology concerns how neuronal circuits are established with precision during development. We are interested in understanding how neural circuits are formed and organized in the vertebrate retina, and in particular how interactions between potential pre- and postsynaptic cells guide this process during development. Although much knowledge has been gained from in vitro work, it is evident that examining this process in vivo will provide insight into the dynamic interactions that take place to establish synaptic specificity. The zebrafish is an ideal model for studying the in vivo development of retinal circuits. This is because synapse formation is completed within a few days after fertilization and the zebrafish embryo can be maintained transparent, making it suitable for in vivo imaging throughout the period of synapse formation and maturation. In this application, we propose to focus on the development of networks in the inner retina. We will determine how outgrowth and elaboration of the postsynaptic dendrites of retinal ganglion cells and the presynaptic terminals of amacrine cells, that together form the first retinal network, contact and form the synaptic region, the inner plexiform layer (IPL) during development. We will combine time-lapse in vivo imaging techniques with molecular approaches to elucidate the normal pattern of IPL development, and then apply these techniques together with the use of retinal mutants to ascertain the role of cell-cell interactions in organizing this synaptic layer. Together, the results of the proposed studies will further our understanding of the mechanisms underlying the structural and functional development of the inner retinal circuitry.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY014358-02
Application #
6696894
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Hunter, Chyren
Project Start
2003-02-01
Project End
2008-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
2
Fiscal Year
2004
Total Cost
$267,750
Indirect Cost
Name
Washington University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Zhang, Chi; Kolodkin, Alex L; Wong, Rachel O et al. (2017) Establishing Wiring Specificity in Visual System Circuits: From the Retina to the Brain. Annu Rev Neurosci 40:395-424
Jorstad, Nikolas L; Wilken, Matthew S; Grimes, William N et al. (2017) Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature 548:103-107
Engerer, Peter; Suzuki, Sachihiro C; Yoshimatsu, Takeshi et al. (2017) Uncoupling of neurogenesis and differentiation during retinal development. EMBO J 36:1134-1146
D'Orazi, Florence D; Zhao, Xiao-Feng; Wong, Rachel O et al. (2016) Mismatch of Synaptic Patterns between Neurons Produced in Regeneration and during Development of the Vertebrate Retina. Curr Biol 26:2268-79
Yoshimatsu, Takeshi; D'Orazi, Florence D; Gamlin, Clare R et al. (2016) Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo. Nat Commun 7:10590
MacDonald, Ryan B; Randlett, Owen; Oswald, Julia et al. (2015) Müller glia provide essential tensile strength to the developing retina. J Cell Biol 210:1075-83
Hoon, Mrinalini; Okawa, Haruhisa; Della Santina, Luca et al. (2014) Functional architecture of the retina: development and disease. Prog Retin Eye Res 42:44-84
Engerer, Peter; Yoshimatsu, Takeshi; Suzuki, Sachihiro C et al. (2014) CentrinFish permit the visualization of centrosome dynamics in a cellular context in vivo. Zebrafish 11:586-7
Yoshimatsu, Takeshi; Williams, Philip R; D'Orazi, Florence D et al. (2014) Transmission from the dominant input shapes the stereotypic ratio of photoreceptor inputs onto horizontal cells. Nat Commun 5:3699
Almeida, Alexandra D; Boije, Henrik; Chow, Renee W et al. (2014) Spectrum of Fates: a new approach to the study of the developing zebrafish retina. Development 141:1971-80

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