IBN-9724155 PI: CHIU A mature nervous system functions in large part because correct synaptic connections are made and maintained between the appropriate groups of neurons. Although we do not fully understand how appropriate connections are established and maintained, it is clear that neuronal networks require bi-directional communication between nerve cells and their synaptic partners. Dr. Chiu has preliminary evidence that the downstream or post-synaptic target can "talk back" and regulate the characteristics of the innervating neuron. Her laboratory has produced a marker that recognizes a molecule found only in mature motor neurons (the specialized nerve cells that directly control the contraction of skeletal muscles). This molecule is interesting for several reasons. First, it is very selective and detected only in this single population of cells, suggesting that the molecule must play an important role in the function of this class of neuron. Second, it appears very late in development, at a time when motor neurons establish their adult pattern of connections with muscle cells. Third, its presence requires an active response from the target muscle. Finally, the molecule is lost when communication between nerve and muscle is disrupted. Together, these results demonstrate that when motor neurons form and maintain active synaptic contact with muscles, they acquire a unique molecule not found in any other cell type. These preliminary results suggest that when muscles are activated, they return a signal to the presynaptic (upstream) neuron; this retrograde signal then confers a biochemical property found only in motor neurons. In this manner, the post-synaptic target can regulate the biochemical nature of its innervating neurons. Dr. Chiu will now investigate how communication between motor neuron and muscle regulates the levels of this molecule, and she will identify and characterize this novel, motor neuron-specific molecule to understand its possible functions in signalling a nd maintaining the normal wiring of the nervous system.