The long term objectives of this work are to contribute to the elucidation of the normal structural organization and development of the vertebrate visual system, and to assess the changes that occur when the system is deprived of normal visual input. The proposed studies are designed to clarify the contributions of specific factors that are likely to play a key role in the establishment of the set of axonal connections characteristic of the mature, vertebrate visual system. In the coming grant period, we propose to examine the following: (1) The development of topographic order in the avian retinotectal projection, with an emphasis on the occurrence of targeting errors, and the abilities of retinal axons that make such errors to respond to positional cues that have been postulated to guide the establishment of topographic order. The formation and fate of aberrant axon branches and arbors will be studied in normal tectum, and in tectal regions deprived of its normal retinal input, to assess the role of positional markers in the process of map refinement. (2) A clarification of the role of a substantial, transient retinofugal projection that appears to act as a """"""""template"""""""" to guide outgrowing axons of the isthmo-optic nucleus, the source of centrifugal innervation of the avian retina, to the target, the contralateral retina, will be undertaken. (3) The establishment of topographic order in the mammalian retinocollicular projection will be studied in normal rats using high resolution anterograde axon tracers. This will serve as a baseline study for an analysis of the role of neural activity in the refinement of the precision of the topographic map between the retina and colliculus. (4) The mechanisms of axon collateral formation and elimination of subcortical projections of the primary visual cortex will be addressed in rats. (5) A heterochronic, homotopic transplant paradigm will be used to test whether """"""""waiting periods"""""""", the phenomenon where axons reach their target but pause for several days prior to extending into it, is related to target immaturity, or may be a feature of axon growth programs.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
7R01EY007025-06
Application #
3263863
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-09-30
Project End
1991-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
005436803
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Kim, J H; Youn, B U; Kim, K et al. (2014) Lhx2 regulates bone remodeling in mice by modulating RANKL signaling in osteoclasts. Cell Death Differ 21:1613-21
McLaughlin, Todd; Lim, Yoo-Shick; Santiago, Alicia et al. (2014) Multiple EphB receptors mediate dorsal-ventral retinotopic mapping via similar bi-functional responses to ephrin-B1. Mol Cell Neurosci 63:24-30
Olsen, Olav; Kallop, Dara Y; McLaughlin, Todd et al. (2014) Genetic analysis reveals that amyloid precursor protein and death receptor 6 function in the same pathway to control axonal pruning independent of ?-secretase. J Neurosci 34:6438-47
Simon, David J; Weimer, Robby M; McLaughlin, Todd et al. (2012) A caspase cascade regulating developmental axon degeneration. J Neurosci 32:17540-53
Feldheim, David A; O'Leary, Dennis D M (2010) Visual map development: bidirectional signaling, bifunctional guidance molecules, and competition. Cold Spring Harb Perspect Biol 2:a001768
Nikolaev, Anatoly; McLaughlin, Todd; O'Leary, Dennis D M et al. (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457:981-9
Lim, Yoo-Shick; McLaughlin, Todd; Sung, Tsung-Chang et al. (2008) p75(NTR) mediates ephrin-A reverse signaling required for axon repulsion and mapping. Neuron 59:746-58
Hoopfer, Eric D; McLaughlin, Todd; Watts, Ryan J et al. (2006) Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 50:883-95
McLaughlin, Todd; O'Leary, Dennis D M (2005) Molecular gradients and development of retinotopic maps. Annu Rev Neurosci 28:327-55
O'Leary, Dennis D M; McLaughlin, Todd (2005) Mechanisms of retinotopic map development: Ephs, ephrins, and spontaneous correlated retinal activity. Prog Brain Res 147:43-65

Showing the most recent 10 out of 40 publications