Abstract

Studies of the chick ciliary ganglion using electrophysiological, molecular, and microscopic techniques are proposed to test two hypotheses. One hypothesis is that extrasynaptic AChRs influence the extent of neuronal survival and maturation during development. A second hypothesis is that presynaptic AChRs, implicated in ACh release, are influenced by neuropeptide-generated signals thereby providing a means of modulating release from nerve terminals. Alpha7 AChRs have been found in ciliary ganglion neurons in addition to synaptic a3 AChRs on the same neurons. Dr. Margiotta proposes to investigate the role of a7 subunits in development by measuring a7 transcripts during the course of development, testing the effects of AChR blockade on neuron survival, maturation, and synapse formation. Presynaptic AChRs will be sought on terminals of cultured and freshly isolated neurons and tested for their effects on ACh release. To examine if synaptic and presynaptic AChRs are targeted by different intracellular signals, the subtype-specific effects of activating separate signaling pathways by neuropeptides will then be elucidated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024417-12
Application #
2685658
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Leblanc, Gabrielle G
Project Start
1994-01-01
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
University of Toledo
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
807418939
City
Toledo
State
OH
Country
United States
Zip Code
43614

  Publications

Conroy, William G; Liu, Qing-Song; Nai, Qiang et al. (2003) Potentiation of alpha7-containing nicotinic acetylcholine receptors by select albumins. Mol Pharmacol 63:419-28
Chen, M; Pugh, P C; Margiotta, J F (2001) Nicotinic synapses formed between chick ciliary ganglion neurons in culture resemble those present on the neurons in vivo. J Neurobiol 47:265-79
Pugh, P C; Margiotta, J F (2000) Nicotinic acetylcholine receptor agonists promote survival and reduce apoptosis of chick ciliary ganglion neurons. Mol Cell Neurosci 15:113-22
McNerney, M E; Pardi, D; Pugh, P C et al. (2000) Expression and channel properties of alpha-bungarotoxin-sensitive acetylcholine receptors on chick ciliary and choroid neurons. J Neurophysiol 84:1314-29
Pardi, D; Margiotta, J F (1999) Pituitary adenylate cyclase-activating polypeptide activates a phospholipase C-dependent signal pathway in chick ciliary ganglion neurons that selectively inhibits alpha7-containing nicotinic receptors. J Neurosci 19:6327-37
Burns, A L; Benson, D; Howard, M J et al. (1997) Chick ciliary ganglion neurons contain transcripts coding for acetylcholine receptor-associated protein at synapses (rapsyn). J Neurosci 17:5016-26
Thornhill, W B; Wu, M B; Jiang, X et al. (1996) Expression of Kv1.1 delayed rectifier potassium channels in Lec mutant Chinese hamster ovary cell lines reveals a role for sialidation in channel function. J Biol Chem 271:19093-8
Margiotta, J F; Pardi, D (1995) Pituitary adenylate cyclase-activating polypeptide type I receptors mediate cyclic AMP-dependent enhancement of neuronal acetylcholine sensitivity. Mol Pharmacol 48:63-71
Howard, M J; Gershon, M D; Margiotta, J F (1995) Expression of nicotinic acetylcholine receptors and subunit mRNA transcripts in cultures of neural crest cells. Dev Biol 170:479-95
Margiotta, J F; Howard, M J (1994) Eye-extract factors promote the expression of acetylcholine sensitivity in chick dorsal root ganglion neurons. Dev Biol 163:188-201

Showing the most recent 10 out of 14 publications