The understanding of how retinal ganglion cells discriminate direction of motion has advanced significantly in recent years, but remains incomplete. A new hypothesis on the mechanisms of retinal directional selectivity postulates that two independent spatially asymmetric pathways converge to the directionally selective ganglion cell. The first facilitates responses to preferred- direction motions and is mediated by an amacrine cell that releases the neurotransmitter acetylcholine. The second inhibits null-direction responses and is mediated by an amacrine cell that releases that neurotransmitter GABA and a bipolar cell that releases glutamate. These two pathways interact locally in individual ganglion-cell dendrites to generate directionally selective responses to motions spanning very short distances. This grant proposal describes three experiments that will scrutinize this hypothesis. The experiments will use On-Off directionally selective ganglion cells of turtles and rabbits. 1) The first experiment will test whether two independent pharmacologically distinct pathways mediate directional selectivity. For this purpose, the investigators will manipulate the retina with pharmacological agents against the neurotransmitters above, while recording the responses of directionally selective ganglion cells. 2) The second experiment will determine whether the synapse between the cholinergic-amacrine and directionally selective ganglion cells has an asymmetric input. To achieve this goal, the investigators will record simultaneously from the amacrine cell that releases acetylcholine and the directionally selective cell. 3) The third experiment will test whether the two putative asymmetric pathways interact locally in dendrites of directionally selective ganglion cells. In this experiment the investigators will image the levels of calcium ions in the dendrites of individual directionally selective ganglion cells. This project should contribute to the understanding of how biophysical mechanisms underlie directional selectivity. Furthermore, the study of retinal directional selectivity will have an impact on the understanding of eye-movement control. Therefore, by elucidating basic brain mechanisms, this project might contribute to finding cures to disorders of the nervous system, and in particular, to those of the visual and oculomotor systems.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY008921-07
Application #
2459129
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1991-08-01
Project End
2001-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Smith-Kettlewell Eye Research Institute
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94115
Segovia, Yolanda; Perez, Rosa María; Grzywacz, Norberto Mauricio et al. (2012) Does Müller Cell Differentiation Occur Prior to the Emergence of Synapses in Embryonic Turtle Retina? J Life Sci (Libertyville) 2012:1200-1205
Cao, Xiwu; Merwine, David K; Grzywacz, Norberto M (2011) Dependence of the retinal Ganglion cell's responses on local textures of natural scenes. J Vis 11:
Ray, Aditi; Sun, Gerald J; Chan, Leanne et al. (2010) Morphological alterations in retinal neurons in the S334ter-line3 transgenic rat. Cell Tissue Res 339:481-91
Barraza, Jose F; Grzywacz, Norberto M (2008) Speed adaptation as Kalman filtering. Vision Res 48:2485-91
Lee, Eun-Jin; Padilla, Monica; Merwine, David K et al. (2008) Developmental regulation of the morphology of mouse retinal horizontal cells by visual experience. Eur J Neurosci 27:1423-31
Chatterjee, Susmita; Merwine, David K; Amthor, Franklin R et al. (2007) Properties of stimulus-dependent synchrony in retinal ganglion cells. Vis Neurosci 24:827-43
Grzywacz, Norberto M; Amthor, Franklin R (2007) Robust directional computation in on-off directionally selective ganglion cells of rabbit retina. Vis Neurosci 24:647-61
Lee, Eun-Jin; Merwine, David K; Padilla, Monica et al. (2007) Choline acetyltransferase-immunoreactive neurons in the retina of normal and dark-reared turtle. J Comp Neurol 503:768-78
Liu, Fan; Merwine, David K; Grzywacz, Norberto M (2006) Statistically robust detection of spontaneous, non-stereotypical neural signals. J Neurosci Methods 153:299-311
Grzywacz, Norberto M; Zucker, Charles L (2006) Modeling Starburst cells' GABA(B) receptors and their putative role in motion sensitivity. Biophys J 91:473-86

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