The long-term goal of the planned investigations is to provide a clearer understanding at the cellular and molecular levels of the roles of neuropeptides as chemical messengers in the nervous system. Studies of the roles of neuropeptides are facilitated by using experimental preparations where both the peptide-secreting neurons and the targets for their actions are well-defined can be investigated from animal to animal at the cell membrane level under nearly physiological conditions. We are using as a main example the neuroendocrine bag cell neurons, located in the abdominal ganglion of the marine mollusk Aplysia. Recent studies indicate that the bag cells function as a multitransmitter system that synthesizes and releases several neuropeptides derived from a common precursor protein. Two of these peptides, egg laying hormone (ELH) and alpha-bag cell peptide, are putative neurotransmitters that modulate activity in identified target neurons for minutes or hours. Two others, beta- and gamma-bag cell peptide we have recently found may mediate other effects. Using combined electrophysiological and biochemical techniques we plan to continue a detailed cellular analysis of the bag cell system in order to unequivocally establish the roles of the neuropeptides as transmitters and to obtain a better understanding of the mechanisms by which the peptides act. In particular, using voltage-clamp techniques we will continue to study the cellular and subcellular mechanisms of action of ELH and alpha-bag cell peptide on identified target neurons. We also plan to study the roles of alpha-, beta- and gamma-BCP as autoexcitatory transmitters which may generate the repetitive impulse discharge of the bag cells, to study conjoint action of peptides on individual neurons, to identify additional bag cell transmitters and to continue to define by biochemical methods the end-products of precursor processing in the bag cells. These studies should result in a clearer understanding of fundamental mechanisms of chemical signaling between neurons and of neuromodulatory systems such as the bag cells that utilize multiple peptides as neurotransmitters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS016490-10
Application #
3396929
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1980-07-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
10
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Begnoche, V L; Moore, S K; Blum, N et al. (1996) Sign stimulus activates a peptidergic neural system controlling reproductive behavior in Aplysia. J Neurophysiol 75:2161-6
Bernheim, S M; Mayeri, E (1995) Complex behavior induced by egg-laying hormone in Aplysia. J Comp Physiol A 176:131-6
Rajpara, S M; Garcia, P D; Roberts, R et al. (1992) Identification and molecular cloning of a neuropeptide Y homolog that produces prolonged inhibition in Aplysia neurons. Neuron 9:505-13
Brown, R O; Pulst, S M; Mayeri, E (1989) Neuroendocrine bag cells of Aplysia are activated by bag cell peptide-containing neurons in the pleural ganglion. J Neurophysiol 61:1142-52
Brown, R O; Mayeri, E (1989) Positive feedback by autoexcitatory neuropeptides in neuroendocrine bag cells of Aplysia. J Neurosci 9:1443-51
Pulst, S M; Gusman, D; Mayeri, E (1988) Immunostaining for peptides of the egg-laying hormone/bag cell peptide precursor protein in the head ganglia of Aplysia. Neuroscience 27:363-71
Jansen, R F; Mayeri, E (1988) The neuropeptide egg-laying hormone modulates multiple ionic currents in single target neurons of the abdominal ganglion of Aplysia. J Neurosci 8:3074-84
Pulst, S M; Rothman, B S; Mayeri, E (1987) Presence of immunoreactive alpha-bag cell peptide[1-8] in bag cell neurons of Aplysia suggests novel carboxypeptidase processing of neuropeptides. Neuropeptides 10:249-59
Brown, R O; Mayeri, E (1987) Central actions of R15, a putative peptidergic neuron in Aplysia. J Neurobiol 18:3-13
Pulst, S M; Gusman, D; Rothman, B S et al. (1986) Coexistence of egg-laying hormone and alpha-bag cell peptide in bag cell neurons of Aplysia indicates that they are a peptidergic multitransmitter system. Neurosci Lett 70:40-5

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