This research covers the function of synaptic transmitters in the visual system. In general, synaptic transmitters affect particular receptive field properties, rather than particular cell types. Generalizations can be made about some transmitters: the fast-acting inhibitory transmitters GABA and glycine affect trigger features such as directional sensitivity and orientation sensitivity, while the excitatory transmitter acetylcholine affects the spontaneous activity and responsiveness of cells. This proposal intends to discover what generalizations can be made about monoamine transmitters (dopamine, noradrenaline, and indoleamines), with investigations on both retina and cortex. A good model for the mammalian retina is the rabbit retina. In order to make generalizations one needs to record from a variety of cell types, and the rabbit retina contains at least 16, which can all be recorded with reasonabale frequency. These cell types include all those found in the cat, and many found in the monkey, with the exception of some of the color coded types. For experiments on light and dark adaptation, however, the cat is preferred, because photopic and scotopic states can be distinguished by spectral sensitivity. In addition to dopamine and indoleamine effects we plan to study the muscarinic effects of acetylcholine, since recent work has suggested that there are muscarinic as well as nicotinic receptors in the retina, and that they may be presynaptic and play a different role. For experiments on the cortex the cat is a good model. Again, the focus will be on the effects of synaptic transmitter agonists and antagonists on the receptive fields of cells. We plan to study the effect of noradrenaline and its agonists and antagonists, looking primarily at properties such as responsiveness and sensitivity, which we have shown are affected by monoamines in the retina. Our overall goal is to describe the general action of synaptic transmitters in the visual system, which will be useful in predicitng the action of various drugs on the visual system. In addition, our data can be put together with data on the anatomical localization and cellular effects of synaptic transmitters to provide a wiring diagram, showing how inputs to a cell are organised to produce the properties of the cell, as we have proposed for the GABA and acetylcholine inputs to directionally selective cells in the retina, giving directional selectivity.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY000053-22
Application #
3255099
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1976-03-01
Project End
1996-02-29
Budget Start
1991-03-01
Budget End
1992-02-29
Support Year
22
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Yang, Yupeng; Fischer, Quentin S; Zhang, Ying et al. (2005) Reversible blockade of experience-dependent plasticity by calcineurin in mouse visual cortex. Nat Neurosci 8:791-6
Fischer, Quentin S; Beaver, Christopher J; Yang, Yupeng et al. (2004) Requirement for the RIIbeta isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity. J Neurosci 24:9049-58
Rao, Yan; Daw, Nigel W (2004) Layer variations of long-term depression in rat visual cortex. J Neurophysiol 92:2652-8
Rao, Yan; Fischer, Quentin S; Yang, Yupeng et al. (2004) Reduced ocular dominance plasticity and long-term potentiation in the developing visual cortex of protein kinase A RII alpha mutant mice. Eur J Neurosci 20:837-42
Shimegi, Satoshi; Fischer, Quentin S; Yang, Yupeng et al. (2003) Blockade of cyclic AMP-dependent protein kinase does not prevent the reverse ocular dominance shift in kitten visual cortex. J Neurophysiol 90:4027-32
Beaver, Chris J; Fischer, Quentin S; Ji, Qinghua et al. (2002) Orientation selectivity is reduced by monocular deprivation in combination with PKA inhibitors. J Neurophysiol 88:1933-40
Reid, S N; Romano, C (2001) Developmental and sensory-dependent changes of group II metabotropic glutamate receptors. J Comp Neurol 429:270-6
Beaver, C J; Ji, Q; Daw, N W (2001) Layer differences in the effect of monocular vision in light- and dark-reared kittens. Vis Neurosci 18:811-20
Beaver, C J; Ji, Q; Fischer, Q S et al. (2001) Cyclic AMP-dependent protein kinase mediates ocular dominance shifts in cat visual cortex. Nat Neurosci 4:159-63
Daw, N W; Gordon, B; Fox, K D et al. (1999) Injection of MK-801 affects ocular dominance shifts more than visual activity. J Neurophysiol 81:204-15

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