The long term goal is to increase understanding of the normal physiological mechanisms of neural communication. Cell cultures of neurons dissociated from the myenteric plexus of rat small intestine provide a simplified system in which to make direct correlation between the physiological and pharmacological properties of a neuron and its content of neuropeptides or other transmitter-related molecules. Neurons in the cultures contain and respond to the major known enteric neurotransmitter candidates (vasoactive intestinal peptide, Substance P, somatostatin, serotonin, met-enkephalin, and acetylcholine) and they form functional synapses. Simultaneous recordings can be made from both neurons of a synaptically connected pair and those same neurons can then be examined immunohistochemically. Cholinergic neurons in the cultures can be subdivided according to their content of co-localized neuropeptides. These subdivisions are physiologically distinguishable with respect to their synaptic actions. At least 3 other subpopulations of neurons, which have non-cholinergic synaptic actions, have also been observed.
Our specific aims are: 1) To use electrophysiological techniques to test whether ( and how) co-localized neuroactive molecules influence the functional properties of interneuronal cholinergic synapses. 2) To immunohistochemically test whether cholinergic neurons contain other enteric co-transmitter candidates. 3) To test neurons making non-cholinergic synapses for content of molecules that mimic their synaptic effects. 4) To use electrophysiological and pharmacological methods to test the mechanisms by which slow synaptic events are generated and to compare the synaptic mechanisms to the effects of exogenously applied transmitter candidates. The major health-relatedness of this work is that better understanding of normal physiological processes is necessary for understanding how these processes go awry in disease. Such understanding may lead to the development of better, more specific treatments of perturbations of neural function caused by disease, injury or aging.
| Fickbohm, D J; Willard, A L (1999) Upregulation of calcium homeostatic mechanisms in chronically depolarized rat myenteric neurons. J Neurophysiol 81:2683-95 |
| Franklin, J L; Willard, A L (1993) Voltage-dependent sodium and calcium currents of rat myenteric neurons in cell culture. J Neurophysiol 69:1264-75 |
| Willard, A L (1992) Excitatory and neurotoxic actions of platelet-activating factor on rat myenteric neurons in cell culture. Ann N Y Acad Sci 664:284-92 |
| Franklin, J L; Fickbohm, D J; Willard, A L (1992) Long-term regulation of neuronal calcium currents by prolonged changes of membrane potential. J Neurosci 12:1726-35 |
| Willard, A L (1990) Substance P mediates synaptic transmission between rat myenteric neurones in cell culture. J Physiol 426:453-71 |
| Willard, A L (1990) A vasoactive intestinal peptide-like cotransmitter at cholinergic synapses between rat myenteric neurons in cell culture. J Neurosci 10:1025-34 |
