The ganglion cells of mammalian retinas exist in roughly a dozen types, each transmitting a different encoding of the visual scene to the brain. The long-term goal of this research is to learn the mechanism by which specific types of ganglion cells achieve these codlings. We have developed an interface incubation system that allows maintenance of multiple samples of adult rabbit retinas for several days in an unsupervised, culture-like system. Genes coding for RNAi or tagged synapse proteins are biolistically transfected into individual retinal ganglion cells. Two questions involve the synaptic events underlying directional selectivity in certain retinal ganglion cells. First, we propose to use RNAi to knock down GABAergic or cholinergic responsiveness in individual ganglion cells. Recording will reveal the contribution of these direct (postsynaptic) inputs to direction selectivity. Second, we will investigate the co-release of GABA and Ach by the starburst amacrine cells. Are the two neurotransmitters released from the same cellular sites or different ones? This will be studied by localizing their vesicular transport proteins. The third question is a more general one. Our recent experiments suggest that the excitatory inputs to ganglion cell dendrites are spatially distributed according to an even-spacing law: the synapses seem to repel each other. In addition, they systematically avoid branch points in the dendritic arbor. We now propose to see if these rules apply to all types of ganglion cells;to model their physiological consequences;and to see if the same rules apply to inhibitory synapses. The methods introduced here can be used in adult animals of any species. They obviate the need for transgenic animals, increase the number of samples that can be simultaneously studied, and allow labeling of proteins that have long half-lives. They can be used in normal tissue or in disease models. We hope that they will be useful to laboratories studying both basic and clinical problems.

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National Eye Institute (NEI)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Greenwell, Thomas
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Massachusetts Eye and Ear Infirmary
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Masland, Richard H (2012) The tasks of amacrine cells. Vis Neurosci 29:3-9
Sun, Daniel; Jakobs, Tatjana C (2012) Structural remodeling of astrocytes in the injured CNS. Neuroscientist 18:567-88
Masland, Richard H (2012) The neuronal organization of the retina. Neuron 76:266-80
Masland, Richard H (2011) Cell populations of the retina: the Proctor lecture. Invest Ophthalmol Vis Sci 52:4581-91
Contini, Massimo; Lin, Bin; Kobayashi, Kazuto et al. (2010) Synaptic input of ON-bipolar cells onto the dopaminergic neurons of the mouse retina. J Comp Neurol 518:2035-50
Sun, Daniel; Lye-Barthel, Ming; Masland, Richard H et al. (2009) The morphology and spatial arrangement of astrocytes in the optic nerve head of the mouse. J Comp Neurol 516:1-19
Lin, Bin; Masland, Richard H; Strettoi, Enrica (2009) Remodeling of cone photoreceptor cells after rod degeneration in rd mice. Exp Eye Res 88:589-99
Lin, Bin; Koizumi, Amane; Tanaka, Nobushige et al. (2008) Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin. Proc Natl Acad Sci U S A 105:16009-14
Jakobs, Tatjana C; Koizumi, Amane; Masland, Richard H (2008) The spatial distribution of glutamatergic inputs to dendrites of retinal ganglion cells. J Comp Neurol 510:221-36
Jakobs, Tatjana C; Ben, Yixin; Masland, Richard H (2007) Expression of mRNA for glutamate receptor subunits distinguishes the major classes of retinal neurons, but is less specific for individual cell types. Mol Vis 13:933-48

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