Two components have been identified in extracts prepared from embryonic eye tissue that influence the long-term fate of chick ciliary ganglion neurons in dissociated cell culture. One of the components, with an apparent molecular weight of about 2x104, stimulates overall growth of the neurons but does not stimulate development of choline acetyltransferase activity. The other component, with an apparent molecular weight of about 5x104, stimulates development of choline acetyltransferase levels but has no effect on neuronal growth. The components will be purified from eye extract and examined both in culture and in vivo to determine whether they serve as target-derived trophic factors for ciliary ganglion neurons. To aid in these studies, monoclonal antibodies will be prepared against the partially purified components and used to purify the components further, manipulate component levels in vivo, and construct quantitative radioimmune assays for the components. Conditions will also be sought which induce the expression of adrenergic properties by the normally cholinergic ciliary ganglion neurons in culture as a way of identifying components which influence the differentiation of neural crest derivatives. Studies will be carried out to determine whether the neurons form chemical and electrical synapses on each other in cell culture, and how such connections are affected by input from neurons of the accessory oculomotor nucleus, the normal preganglionic input to ciliary ganglion neurons. Bgt 3.1, a protein neurotoxin present as a minor component in B. multicinctus venom, reversibly blocks acetylcholine (ACh) sensitivity on ciliary ganglion neurons and, in a separate action, induces the internalization of Alpha-bungarotoxin bound to the neurons. Alpha-Bungarotoxin does neither of these. Bgt 3.1 will be radiolabeled and examined as a possible ligand for the neuronal ACh receptor. If suitable, it will be used to study regulation of the neuronal receptor. Also, ultrastructural studies will be carried out to determine the distribution of Alpha-bungarotoxin binding sites during development since they do not appear to be associated with synaptic regions at early times, and to follow the path of bound Alpha-bungarotoxin that is internalized by Bgt 3.1 treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS012601-14
Application #
3394913
Study Section
Neurology C Study Section (NEUC)
Project Start
1979-05-01
Project End
1994-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Thakar, Sonal; Wang, Liqing; Yu, Ting et al. (2017) Evidence for opposing roles of Celsr3 and Vangl2 in glutamatergic synapse formation. Proc Natl Acad Sci U S A 114:E610-E618
Dulcis, Davide; Lippi, Giordano; Stark, Christiana J et al. (2017) Neurotransmitter Switching Regulated by miRNAs Controls Changes in Social Preference. Neuron 95:1319-1333.e5
Zhang, Ying; Cao, Shu-Xia; Sun, Peng et al. (2016) Loss of MeCP2 in cholinergic neurons causes part of RTT-like phenotypes via ?7 receptor in hippocampus. Cell Res 26:728-42
Ni, Kun-Ming; Hou, Xiao-Jun; Yang, Ci-Hang et al. (2016) Selectively driving cholinergic fibers optically in the thalamic reticular nucleus promotes sleep. Elife 5:
Lippi, Giordano; Fernandes, Catarina C; Ewell, Laura A et al. (2016) MicroRNA-101 Regulates Multiple Developmental Programs to Constrain Excitation in Adult Neural Networks. Neuron 92:1337-1351
John, Danielle; Berg, Darwin K (2015) Long-lasting changes in neural networks to compensate for altered nicotinic input. Biochem Pharmacol 97:418-424
Duan, Jing-Jing; Lozada, Adrian F; Gou, Chen-Yu et al. (2015) Nicotine recruits glutamate receptors to postsynaptic sites. Mol Cell Neurosci 68:340-9
Halff, Andrew W; Gómez-Varela, David; John, Danielle et al. (2014) A novel mechanism for nicotinic potentiation of glutamatergic synapses. J Neurosci 34:2051-64
Gomez-Varela, David; Berg, Darwin K (2013) Lateral mobility of presynaptic ?7-containing nicotinic receptors and its relevance for glutamate release. J Neurosci 33:17062-71
Wang, Xulong; Lippi, Giordano; Carlson, David M et al. (2013) Activation of ?7-containing nicotinic receptors on astrocytes triggers AMPA receptor recruitment to glutamatergic synapses. J Neurochem 127:632-43

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