Bipolar cells convey information from photoreceptors to amacrine and ganglion cells. These interneurons not only relay visual information from distal to proximal retina, but also decompose it. Some of this decomposition occurs in the dendrites of bipolar cells, creating ON and OFF bipolar cells or transient and sustained bipolar cells. But the information reaching the proximal retina is probably further decomposed as it leaves the bipolar cell axon terminal. The objectives of this proposal are to examine this decomposition at the output synapses of bipolar cells. The rationale is that bipolar cell subtypes encode specific information about the visual scene. The hypothesis is that a variety of mechanisms control the bipolar cell output synapse and that this contributes to the information decomposition. The model is that amacrine cells and ganglion cells integrate an array of bipolar cell outputs which are shaped by presynaptic parameters at the axon terminal. The first specific aim of this proposal is to examine the function of subtypes of presynaptic calcium channels in the relay of visual information. The second specific aim will examine the function of autoreceptor feedback and amacrine cell feedback on bipolar cell transmitter release. The hypothesis is that the feedback has different effects on the various calcium channels that mediate transmitter release. The third specific aim will be to determine the effect of large conductance (BK) channels at the bipolar cell synapse and whether calcium channels subtypes are differentially affected. The final specific aim will evaluate the function of internal calcium stores in modulating bipolar cell transmitter release. It will test the hypothesis that internal calcium potentiates release but does not induce transmitter release. The role of these mechanisms in establishing the visual information reaching the ganglion cell will be explored. Overall, the experiments are designed to determine the spectrum of bipolar cell release mechanisms and how they determine the visual channels used to encode vision. ? ?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY005725-25
Application #
7345360
Study Section
Biology and Diseases of the Posterior Eye Study Section (BDPE)
Program Officer
Greenwell, Thomas
Project Start
1984-08-01
Project End
2009-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
25
Fiscal Year
2008
Total Cost
$364,531
Indirect Cost
Name
State University of New York at Buffalo
Department
Physiology
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Garaycochea, Jay; Slaughter, Malcolm M (2016) GABAB receptors enhance excitatory responses in isolated rat retinal ganglion cells. J Physiol 594:5543-54
Wu, Fuguo; Kaczynski, Tadeusz J; Sethuramanujam, Santhosh et al. (2015) Two transcription factors, Pou4f2 and Isl1, are sufficient to specify the retinal ganglion cell fate. Proc Natl Acad Sci U S A 112:E1559-68
Sethuramanujam, Santhosh; Slaughter, Malcolm M (2014) Disinhibitory recruitment of NMDA receptor pathways in retina. J Neurophysiol 112:193-203
Li, Ping; Slaughter, Malcolm M (2012) Gating effects on picrotin block of glycine receptors. Neuroreport 23:1017-20
Song, Yunbo; Slaughter, Malcolm M (2010) GABA(B) receptor feedback regulation of bipolar cell transmitter release. J Physiol 588:4937-49
Duan, Lei; Yang, Jaeyoung; Slaughter, Malcolm M (2009) Caffeine inhibition of ionotropic glycine receptors. J Physiol 587:4063-75
Frolov, R V; Slaughter, M M; Singh, S (2008) Effects of celecoxib on ionic currents and spontaneous firing in rat retinal neurons. Neuroscience 154:1525-32
Shen, W; Slaughter, M M (2001) Multireceptor GABAergic regulation of synaptic communication in amphibian retina. J Physiol 530:55-67
Tian, N; Slaughter, M M (1994) Pharmacology of the GABAB receptor in amphibian retina. Brain Res 660:267-74
Tian, N; Slaughter, M M (1994) Pharmacological similarity between the retinal APB receptor and the family of metabotropic glutamate receptors. J Neurophysiol 71:2258-68

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