The long-term objective of this proposal is to understand the cellular mechanisms underlying naturally occurring synapse elimination at the neuromuscular junction. Presently we have only an incomplete understanding of this form of synaptic plasticity. The difficulty is largely technical and due to lack of approaches that can reveal the sequence of cellular and molecular events that underlie synapse elimination. Evidence from the recently developed techniques I used in my studies this past year and a half (supported by NRSA) indicate that synapse elimination is spatially regulated to a remarkable degree. Within a neuromuscular junction, branches of the losing axon closest to the other axon are eliminated before ones that are more distant. The loss of nerve terminal branches is associated with a nearly contemporaneous disassembly of the postsynaptic specialization.
The specific aim of this fellowship is to use a new vital staining technique to allow high temporal and spatial resolution monitoring of both the pre-and post-synaptic apparatus as synapse elimination proceeds. Our hope is that this study will provide insights into not only synaptic competition at the neuromuscular junction but also analogous events in the central nervous systems responsible for life long changes in synaptic circuitry such as learning and memory.
