The proposed research is designed to obtain a basic understanding of the electrophysiology, pharmacology and morphology of mammalian parasympathetic ganglia and to define the local neuronal interactions which contribute to the integrative function of autonomic ganglia, in general. Local neuronal interactions which occur during ganglionic transmission will be analyzed in cat vesical pelvic ganglia (VPG) using intracellular, single electrode voltage clamp, and iontophoretic techniques coupled with differential interference microscopy. The following local neuronal interactions will be investigated in mammalian parasympathetic ganglia 1) the muscarinic inhibitory and excitatory slow synaptic potentials 2) the late slow modulatory potentials 3) synaptic events underlying synaptic plasticity, 4) intrinsic cell-to-cell communication and 5) the neurotransmitter/neuromodulatory role of leucine-enkephalin. The sites, mechanisms and functional significance of the local neuronal interactions which occur in bladder ganglia will be determined. Analysis of the mechanisms underlying these local neuronal interactions may lead to a better understanding of autonomic function, in general, as well as """"""""higher"""""""" brain functions involved in memory, learning, and behavior. In addition, the information obtained from pharmacologicaly analysis of these synaptic mechanisms may eventually result in use of drugs which are more clinically effective in the treatment of CNS disorders, in particular, Parkinson's Disease as well as autonomic dysfunction, especially, bladder dysfunction.
