A Regulatory Loop at the Neuromuscular Junction

Wayne State University, Detroit MI

Investigators

Abstract

IBN-0092623 Loeb Title: A Regulatory Loop at the Neuromuscular Junction Synapses are the nodes of communication between cells in the nervous system. Their precise position and function enables us to perform tasks as simple as moving our limbs, and as complex as formulating new memories and ideas. The neuromuscular junction, or synapse between a spinal cord motor neuron and a muscle cell, is by far one of the largest and simplest to study. During development, proper synapse formation requires ongoing nerve-muscle electrical activity. Without this activity, synapses fail to form properly. The purpose of Dr. Loeb's project is to determine what are the molecular factors that regulate the formation of synapses and how normal synaptic activity orchestrates these factors. Dr. Loeb's hypothesis is that regulatory factors are released both from the muscle cell and the neuron in response to the degree of electrical activity of the synapse and that these factors, in turn, have regulatory effects on each other that ultimately bring together necessary synaptic building blocks. It will be studied how disrupting electrical activity of the synapse during synapse development modulates the production of two families of regulatory factors: the neuregulins, expressed in neurons, and the neurotrophins, expressed in muscle. Dr. Loeb will also use a model system in the chick embryo that prevents the development of the limb on one side to see the effects of neurotrophic factors derived from that limb on the expression of neuregulins in neurons. From these studies, Dr. Loeb hopes to generate a unifying hypothesis of how synapses are formed and how this process is fine-tuned during development.