DEVELOPMENT OF FUNCTION IN THE VERTEBRATE RETINA

University Of California San Francisco, San Francisco CA

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Abstract

Retinal development is controlled by both genetic lineage and extracellular factors. The identity and mechanisms of action of these factors is generally unknown, but recent experimental results suggest that neurotransmitter molecules may play a regulatory role in the the maturation of retinal neurons. The objective of the research proposed here is to determine the role that neurotransmitter molecules or their ion channel receptors play in the maturation of ganglion cells. This objective will be pursued in electrophysiologicla and anatomical studies of the retina in rainbow trout. Teleost fish are unique among vertebrates because their eyes continue to grow throughout the life of the animal. New retinal differentiation occurs continually at the margin of the mature retinal. This ring of newly developing retina is the peripheral germinal zone (PGZ). In the PGX there is a gradient of development that extends continuously from undifferentiated stem cells at the margin to fully mature cells more centrally. Thus, in the PGZ at any given moment, age and distance are equivalent and all stages of retinal differentiation and maturation exist side by side. This offers experimental advantages unmet in mammalian systems. The specific aims of the research plan are: To determine that changes in the structure of the dendritic arbor of ganglion cells associated with their developmental maturation in the PGZ. To determine the role of glutamate and acetylcholine as regulators of these changes. In particular, to establish whether regulation is dependent on the presynaptic release of the neurotransmitters or the development of postsynaptic ion channel receptors. To determine whether these postsynaptic receptor undergo functional changes associated with the maturation of ganglion cells and to explore the role that these functional changes may have in controlling developmental events. Finally, to establish whether the neurotransmitters or their receptors are the cause of changes associated with maturation by investigating the consequence to retinal development of interfering with the normal changes in the neurotransmitter systems.