Sensory stimulation can alter the behavior of an animal for many hours. Relatively little is, as yet, known of the neural and molecular mechanisms that underlie such long-lasting changes in behavior. This project will investigate prolonged changes in excitability and neuropeptide secretion in the bag cell neurons of Aplysia, a group of cells that controls reproductive behaviors lasting several hours. In response to brief synaptic stimulation, these neurons generate a 30 minute afterdischarge, which is followed by a period of inhibition that persists for 18 hrs. During the afterdischarge, there is a progressive potentiation of the release of neuropeptides. The first set of experiments will examine the role of an alpha1A voltage-dependent calcium channel subunit in this potentiation of secretion. In particular, experiments will test the hypothesis that, during potentiation, this channel is rapidly transferred from intracellular organelles to the plasma membrane at sites of neuropeptide release. The second set of experiments will assess the role of an apparently novel intracellular calcium store in neuropeptide secretion. This store can be mobilized by activation of the insulin receptor, which triggers neuropeptide release. Finally, the basis for the prolonged inhibition of excitability and secretion that follows an afterdischarge will be investigated. Experiments will test whether a non-selective cation channel that is activated by a protein tyrosine phosphatase contributes to the depolarization that drives the afterdischarge. Patch clamp studies of this channel, and of potassium channels, combined with intracellular injection of enzymes, will determine whether this channel is modified during the inhibited state, or whether stimulation fails to activate the enzymes needed to induce a long-lasting afterdischarge.
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