Role of P2X and P2Y ATP Receptors in Neuromuscular Development

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0077634HumeNerve cells communicate information to each other at narrow zones of contactreferred to as synapses. The incoming presynaptic cell releases a chemicalsignal (the neurotransmitter), which binds to receptors on the target cell,eliciting electrical excitation or inhibition. The general goal of theseexperiments is to understand the mechanisms that allow developing synapsesto reach their stable, mature state. The principal hypothesis to be exploredis that in addition to the two signals known to pass between nerve andmuscle to promote synapse maturation (agrin and ARIA), an additionalsignaling system also transmits key information. This proposed signalingsystem consists of ATP (adenosine 5' triphosphate) released from presynapticterminals interacting with two different types of ATP receptors on themuscle cell surface. The hypothesis will be tested by using molecularbiological and pharmacological tools to alter the function of the ATPreceptors on the surface of chick muscle cells developing within the egg,and in cell culture.It is important that mature neuromuscular synapses be stable, so that theycan reliably control of the routine actions of the nervous system such ascommanding muscles to move in the pattern that allows us to breathe.However, understanding the mechanisms that promote synaptic growth andmaturation are likely to also provide us with insight into the mechanismsthat bring about changes in synaptic function in other regions of the maturenervous system where synapses are not always stable. Changes in theamplitude of synaptic responses are thought to be the cellular basis bywhich learning and forgetting occur.