The Edinger Westphal (EW) - ciliary ganglion (CG) pathway controls accommodation, iris constriction, and possibly blood flow in the choroid and as such, is important for normal eye function and clinical diagnosis. The longterm objective of this project is to identify the factors which influence the formation and maintenance of synaptic contacts between EW and CG neurons. Experiments will use a well established culture system combined with intracellular electrophysiology and immunohistochemistry to determine what elements contribute to the development of EW terminal morphology as well as to the formation of functional synapses with CG neurons. Previous work has found that calyx-like contacts, which mimic the unusual cup-shaped morphology of EW calyciform terminals in vivo, are found preferentially on CG neurons when EW neurons are cultured together with both dorsal root ganglion and CG neurons. The specificity of this interaction is an unusual departure from the promiscuity often displayed by neurons in vitro and may yield new insights into the process of synaptic terminal morphogenesis. For this reason, this project focusses on the formation of these calyx-like contacts as well as on the formation of functional synapses between EW and CG neurons in vitro. There are five specific aims which address the following five sets of questions: (1) What morphological and physiological characteristics of EW calyciform synaptic terminals are expressed in culture? (2) What distinctions between subpopulations of CG neurons are retained in culture? Are calyx-like contacts limited to a specific subpopulation of CG neurons as they are in the ganglion? (3) To what extent is the identity of the presynaptic neuron involved in synaptic specificity? Can EW neurons compete with inappropriate inputs and displace them in the formation of synapses and calyx-like contacts on CG neurons? Can CG neurons elicit calyx-like morphology from any presynaptic neuron? (4) Do EW and CG neurons acquire the ability to form or elicit calyx-like morphology at a particular developmental stage? (5) Are electrical activity and/or neurotransmitter mediated interactions required for the formation of calyx-like contacts between EW and CG neurons in vitro?

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY009768-01
Application #
3267153
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1992-08-01
Project End
1995-07-31
Budget Start
1992-08-01
Budget End
1993-07-31
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
McAvoy, M; Smith, M A; Fujii, J T (1996) Agrin mRNA expression in the developing chick Edinger-Westphal nucleus. Vis Neurosci 13:293-301
Fujii, J T; Su, F T; Woodbury, D J et al. (1996) Plasma membrane calcium ATPase in synaptic terminals of chick Edinger-Westphal neurons. Brain Res 734:193-202
Fujii, J T; Lucaj, Z; Peduzzi, J D et al. (1995) Development of parvalbumin immunoreactivity in the chick Edinger Westphal nucleus. J Comp Neurol 360:612-20
Fujii, J T (1994) Synaptic vesicle proteins and target-dependent morphogenesis of calyx-like contacts in vitro. Exp Neurol 129:155-62
Lucaj, Z; Fujii, J T (1994) Multiple subtypes of voltage-gated calcium currents in the Edinger-Westphal nucleus. Brain Res 660:1-7
Fujii, J T; Knapp, P E (1994) Characterization and development of glial and other non-neuronal cells in chick Edinger Westphal cultures. Brain Res Dev Brain Res 78:217-25