Synapses are the functional points of interaction between neurons, where information in one neuron is passed onto and processed by another. At some synapses, action potentials cause secretion of transmitter with a high efficacy, and a train of action potentials rapidly depletes the readily releasable pool of vesicles resulting in the diminishing responses of synaptic depression. At other synapses, release to single action potentials can be rare, while the probability of release facilitates in a train of action potentials. This project will explore why some synapses are strong, but weaken on use, while others are initially weak, but become stronger on use.
Crayfish neuromuscular junctions are functionally similar to mammalian central nervous system synapses while offering significant advantages. At leg extensor muscles, phasic motor neuron synapses transmit strongly and show depression, while tonic motor neuron synapses initially transmit extremely weakly but facilitate tremendously. Previous work showed both synapses to be structurally similar, to admit similar amounts of Ca2+ per action potential, and to have similar numbers of vesicles available for release to a train of action potentials. Phasic and tonic synapses differ dramatically in their secretory responses to steps of presynaptic calcium concentration ([Ca2+]i) evoked by photolysis of photosensitive calcium buffers (liberation of "caged calcium"). A computational model was constructed in which the differences between phasic and tonic synapses are due to vesicles at tonic synapses being less likely to be "primed" and ready for immediate release, while [Ca2+]i accumulating in an action potential train primes vesicles for later release. The goal of this project is to test this model, and revise or refine it as necessary, to gain a more complete understanding of this crucial form of regulation of synaptic strength and plasticity.
The project will involve the training of junior scientists to assume independent posts in research and university teaching, the teaching of specialized techniques to graduate students, exposure of undergraduates to and involvement in the scientific research process, and the training of secondary teachers in the scientific method and research procedures. Minority and women students and scientists have been and will continue to be recruited as participants. Collaborations with domestic and foreign scientists are proposed. Active participation in national and international scientific forums will be pursued. In addition, specialized techniques of broad use in biology will be refined.
