The overall objective of the proposed research program is to further our understanding of the functional and structural development of retinal ganglion cells, the neurons that convey all information from the eyes to the visual centers of the brain.
Five specific aims are proposed designed to fill major gaps in our current knowledge. As the first specific aim, patch-clamp recordings will be made from developing ganglion cells of the ferret in conjunction with their intracellular filling to allow for the morphological assessment of cells into major classes (alpha, beta and gamma) as well as On, Off and On-Off subtypes. Spontaneous activity patterns will be recorded at three well-defined stages of development and quantitative methods will be used to assess discharge patterns.
The aim of this study is to determine whether different classes of cells manifest class-specific spontaneous activity patterns during the developmental period when activity mediated refinements are known to occur at retinorecipient structures. The second specific aim is to determine whether two intrinsic membrane properties studied during the past grant period (speed of recovery from Na-channel inactivation and Ca-mediated potassium currents) relate to the spontaneous activity patterns manifested by developing ganglion cells. The third specific aim is to determine how the visual responses of developing ganglion cells to flashing spots of light correlate with the stratification of dendrites in these neurons. In particular, we want to learn whether immature ganglion cells with dendrites ramifying within both the On and Off sublaminae of the developing IPL respond to the onset as well as the offset of flashing spots of light. The third specific aim is to determine whether the functional circuitry underlying On and Off responses in the developing retina is equivalent to that found in the mature retina. For this purpose, we will assess the effects of APB application on the light-evoked responses of morphologically identified ganglion cells. This glutamate agonist selectively blocks On responses in the mature retina, but preliminary results indicate that both On and Of f pathways can be effectively blocked by this drug in multistratified ganglion cells of the developing retina. The fifth specific aim is to determine whether cholinergic amacrine cells play a role in the formation of segregated On- and Off-cone bipolar cell axonal projections and in the stratification of retinal ganglion cell dendrites. To address this issue we have devised a novel method for eliminating cholinergic amacrine cells from the developing retina. The successful completion of this research program will provide new insights into the development of the mammalian retina, and it will also have implications for elucidating the cellular mechanisms underlying the formation of neuronal connections at higher levels of the nervous system.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY003991-19
Application #
6326216
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Hunter, Chyren
Project Start
1982-08-01
Project End
2006-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
19
Fiscal Year
2001
Total Cost
$369,063
Indirect Cost
Name
University of California Davis
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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Dursun, Ilknur; Jakubowska-Dogru, Ewa; Elibol-Can, Birsen et al. (2013) Effects of early postnatal alcohol exposure on the developing retinogeniculate projections in C57BL/6 mice. Alcohol 47:173-9
Dursun, Ilknur; Jakubowska-Dogru, Ewa; van der List, Deborah et al. (2011) Effects of early postnatal exposure to ethanol on retinal ganglion cell morphology and numbers of neurons in the dorsolateral geniculate in mice. Alcohol Clin Exp Res 35:2063-74
Rubin, Carol M; van der List, Deborah A; Ballesteros, Jose M et al. (2011) Mouse mutants for the nicotinic acetylcholine receptor ß2 subunit display changes in cell adhesion and neurodegeneration response genes. PLoS One 6:e18626
Speer, Colenso M; Sun, Chao; Chapman, Barbara (2011) Activity-dependent disruption of intersublaminar spaces and ABAKAN expression does not impact functional on and off organization in the ferret retinogeniculate system. Neural Dev 6:7
Murray, Karl D; Rubin, Carol M; Jones, Edward G et al. (2008) Molecular correlates of laminar differences in the macaque dorsal lateral geniculate nucleus. J Neurosci 28:12010-22
Gunhan, Emine; Swe, Mimi; Palazoglu, Mine et al. (2008) Expression and purification of cysteine introduced recombinant saporin. Protein Expr Purif 58:203-9
Sun, Chao; Speer, Colenso M; Wang, Guo-Yong et al. (2008) Epibatidine application in vitro blocks retinal waves without silencing all retinal ganglion cell action potentials in developing retina of the mouse and ferret. J Neurophysiol 100:3253-63
Sun, Chao; Warland, David K; Ballesteros, Jose M et al. (2008) Retinal waves in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor. Proc Natl Acad Sci U S A 105:13638-43

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