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.
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