Mechanisms Controlling the Function and Development of Neuronal Nicotinic Synapses

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Synapses are specialized cell junctions that link neurons into functional networks, thereby providing the basis of all integrative neural signaling. Synaptic transmission involves release of neurotransmitter from presynaptic neuron terminals and capture by specific postsynaptic receptors that transit ions to alter the target cell's excitability. Nicotinic acetylcholine (ACh) receptors (nAChRs) bind ACh to mediate excitatory synaptic transmission in autonomic ganglia controlling homeostasis and modulating the output of brain circuits that control coordinated movement and behaviors underlying pleasure and reward. Despite their broad relevance, the molecular mechanisms regulating function and development of nicotinic synapses remain poorly understood. This project will explore changes triggered by a neuropeptide (PACAP) released from the pituitary at nicotinic synapses on autonomic ciliary ganglion (CG) neurons. Recent findings indicate that PACAP rapidly regulates synapses on CG neurons in culture. Electrophysiological, imaging, and biochemical approaches will be used to identify altered synaptic properties and determine the protein-protein interactions that mediate this regulation. Since PACAP levels are developmentally regulated, and exogenous PACAP enhances neuronal survival in an activity dependent fashion, the possibility that PACAP persistently influences synapse formation and function will also be explored. It is expected that PACAP-triggered signaling will be critical both for building nicotinic synapses and controlling their function. Lastly, outreach programs administered through the University of Toledo will be used to train visiting undergraduates, high school students, and high school teachers. Thus, this project will further elucidate molecular mechanisms relevant to homeostatic regulation, behavior, and development while simultaneously fostering the scientific literacy and training of underrepresented groups.