(from the principal investigator's proposal): The long-term goals of these studies are to understand how optic nerves and other axons of the central nervous system form accurate synaptic connections during development and how optic nerves of adult humans might successfully respond to injury and regenerate. For this, the adult goldfish is used as a model because its optic nerve can regenerate to reform a precise projection into the brain while utilizing impulse activity and other cellular cues common to mammalian development.
Four specific aims are proposed. The first uses nanoliter injections of a fluorescent tracer, DiI, to label axons from neighboring retinal ganglion cells visualized in tectal whole mounts. These are examined at various times during regeneration and after various pharmacologic manipulations such as blockade of impulse activity and stimulation of neurotransmitter receptors to determine the structural changes and events associated with the reformation of fine retinotopic order.
The second aim uses similar labeling but visualizes regenerating axons in the living fish for 6 h to 4 d to understand the dynamic events associated with regeneration and to perform real time pharmacological experiments on growing axons for the first time in an adult vertebrated.
The third aim will use retinal explants in culture to compare the dynamics and pharmacological responses of optic axons regenerating in the isolation of tissue culture with that seen in the animal.
The fourth aim i s to determine the pattern and amount of activity expressed by regenerating optic fibers using electrophysiological recording since this activity may be important for determining synaptic connections and since the information will be needed to interpret and perform the preceding experiments.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY006746-15
Application #
2160900
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1986-06-01
Project End
1997-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
15
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Anatomy/Cell Biology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697
Fawcett, J W; Housden, E; Smith-Thomas, L et al. (1989) The growth of axons in three-dimensional astrocyte cultures. Dev Biol 135:449-58
Meyer, R L (1987) Intratectal targeting by optic fibers in goldfish under impulse blockade. Brain Res 465:115-24