In vivo, functional interactions between the immune and nervous systems have been widely studied in recent years. Our own research focuses on neuroimmunological interactions at the cellular level in vitro. We have discovered a novel form of a neuroimmunological communication - a long- lasting (hrs) enhancement in the efficacy of synaptic transmission in autonomic ganglia produced by immunological activation of ganglionic mast cells. Our current goal is to establish the nature of the signal molecules and the cellular mechanisms underlying antigen-induced physiological changes in synaptic transmission. We propose to continue combining electrophysiological, immunological and biochemical techniques to define the processes by which immunologic activation of mast cells within the guinea pig superior cervical ganglion (SCG) produces both fleeting and sustained increases in synaptic efficacy. Studies will be carried out to: (1) define the biophysical mechanisms and cellular locus (pre- vs. postsynaptic) underlying antigen-induced long-term potentiation; (2) identify the signal molecules responsible for antigen- induced physiological changes, using extracts prepared from immunologically stimulated purified mast cells and pharmacologic reagents and (3) study SCG from mast cell-deficient mouse strains to test whether cells in sympathetic ganglia other than mast cells participate in antigen-induced neurophysiological changes. We further propose to extend our findings in the SCG to the exploration of the inferior mesenteric ganglion (IMG), where immunoregulation of a peripheral reflex (distal colon - IMG) can be investigated in vitro. Studies will be conducted to examine the cellular electrophysiological effects of immunologic activation of mucosal-type mast cells in the colon, or connective tissue-type mast cells in IMG, on neurons participating in reflex activity. These studies will add to our understanding of synaptic plasticity in sympathetic ganglia, and they will further define functional mechanisms of interaction between the immune and nervous systems at the level of the cell. These observations should provide a valuable base for further insights into the pathophysiology of the myriad diseases associated with immediate hypersensitivity reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025598-06
Application #
2265594
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-02-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1996-04-30
Support Year
6
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Pharmacology
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Cavalcante de Albuquerque, A A; Leal-Cardoso, J H; Weinreich, D (1996) Antigen-induced synaptic plasticity in sympathetic ganglia from actively and passively sensitized guinea-pigs. J Auton Nerv Syst 61:139-44
Weinreich, D; Undem, B J; Taylor, G et al. (1995) Antigen-induced long-term potentiation of nicotinic synaptic transmission in the superior cervical ganglion of the guinea pig. J Neurophysiol 73:2004-16
Christian, E P; Weinreich, D (1992) Presynaptic histamine H1 and H3 receptors modulate sympathetic ganglionic synaptic transmission in the guinea-pig. J Physiol 457:407-30
Weinreich, D; Undem, B J; Leal-Cardoso, J H (1992) Functional effects of mast cell activation in sympathetic ganglia. Ann N Y Acad Sci 664:293-308
Undem, B J; Myers, A C; Weinreich, D (1991) Antigen-induced modulation of autonomic and sensory neurons in vitro. Int Arch Allergy Appl Immunol 94:319-24
Myers, A C; Undem, B J; Weinreich, D (1991) Influence of antigen on membrane properties of guinea pig bronchial ganglion neurons. J Appl Physiol 71:970-6
Undem, B J; Hubbard, W C; Christian, E P et al. (1990) Mast cells in the guinea pig superior cervical ganglion: a functional and histological assessment. J Auton Nerv Syst 30:75-87
Myers, A C; Undem, B J; Weinreich, D (1990) Electrophysiological properties of neurons in guinea pig bronchial parasympathetic ganglia. Am J Physiol 259:L403-9
Undem, B J; Myers, A C; Barthlow, H et al. (1990) Vagal innervation of guinea pig bronchial smooth muscle. J Appl Physiol 69:1336-46
Christian, E P; Undem, B J; Weinreich, D (1989) Endogenous histamine excites neurones in the guinea-pig superior cervical ganglion in vitro. J Physiol 409:297-312

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