This is an electrophysiological and anatomical investigation of the activity dependence of synapse elimination both during regeneration (as a model for development) and in the mature retinotectal projection of goldfish. It seeks to understand the role of activity in setting up and maintaining precise orderly connections, and takes advantage of four features of this system: 1) the ease of surgical manipulation in adult fish, 2) the ability of the optic fibers to regenerate a precise retinotopic projection, 3) the geometry of the eye which allows the containment of tetrodotoxin for long term block of activity and 4) the known nicotinic cholinergic pharmacology of retinotectal transmission in fish and frogs which allows blocking of synaptic transmission. The working hypothesis is that correlated activity, a property of near neighbors in the retina, is used as a cue to concentrate the initial diffusely regenerated arbors into correct areas in the overall map. This will be tested by 1) blocking all activity with TTX, 2) synchronizing all activity with strobe light or 3) blocking all transmission with continuous AlphaBungarotoxin application to the tectum during regeneration; and assessing targeting of arbors via electrophysiological mapping and single fiber HRP fills in whole mounts. Local blocking experiments with AlphaBungarotoxin show that arbors move out of blocked regions to make effective synapses elsewhere. This will be further investigated with the single fiber whole mount technique and also quantitatively at the electron microscopic level. There are two health related aspects. First the phenomenon of activity dependent synaptic stabilization and competition in neural development is germane to developmental disorders such as amblyopia. Secondly the failure of axonal regeneration in mammalian central nervous system makes most neurological damage irreversible. Better understanding of successful regeneration in lower vertebrates may lead to strategies for therapeutic restoration of this ability in humans.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003736-10
Application #
3258165
Study Section
Visual Sciences B Study Section (VISB)
Project Start
1981-05-01
Project End
1992-04-30
Budget Start
1990-05-01
Budget End
1991-04-30
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
State University of New York at Albany
Department
Type
Schools of Arts and Sciences
DUNS #
City
Albany
State
NY
Country
United States
Zip Code
12222
Schmidt, John T; Morgan, Patricia; Dowell, Natalie et al. (2002) Myosin light chain phosphorylation and growth cone motility. J Neurobiol 52:175-88
Schmidt, J T; Buzzard, M; Borress, R et al. (2000) MK801 increases retinotectal arbor size in developing zebrafish without affecting kinetics of branch elimination and addition. J Neurobiol 42:303-14
Zhang, C; Schmidt, J T (1999) Adenosine A1 and class II metabotropic glutamate receptors mediate shared presynaptic inhibition of retinotectal transmission. J Neurophysiol 82:2947-55
Schmidt, J T; Schachner, M (1998) Role for cell adhesion and glycosyl (HNK-1 and oligomannoside) recognition in the sharpening of the regenerating retinotectal projection in goldfish. J Neurobiol 37:659-71
Zhang, C; Schmidt, J T (1998) Adenosine A1 receptors mediate retinotectal presynaptic inhibition: uncoupling by C-kinase and role in LTP during regeneration. J Neurophysiol 79:501-10
Schmidt, J T (1998) Up-regulation of protein kinase C in regenerating optic nerve fibers of goldfish: immunohistochemistry and kinase activity assay. J Neurobiol 36:315-24
Jian, X; Szaro, B G; Schmidt, J T (1996) Myosin light chain kinase: expression in neurons and upregulation during axon regeneration. J Neurobiol 31:379-91
Schmidt, J T; Lemere, C A (1996) Rapid activity-dependent sprouting of optic fibers into a local area denervated by application of beta-bungarotoxin in goldfish tectum. J Neurobiol 29:75-90
Schmidt, J T (1995) The modulatory cholinergic system in goldfish tectum may be necessary for retinotopic sharpening. Vis Neurosci 12:1093-1103
Jian, X; Hidaka, H; Schmidt, J T (1994) Kinase requirement for retinal growth cone motility. J Neurobiol 25:1310-28

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