View Program - 63rd Annual Drosophila Research Conference

The hallmark of neurodegenerative diseases such as Alzheimer’s Disease (AD), Parkinson’s. Disease (PD), and Amyotrophic Lateral Sclerosis (ALS) is the loss of neurons. However, recent evidence suggests that synapse dysfunction occurs long before clinical symptoms are manifested. Although PD and AD are the most prevalent neurodegenerative diseases, ALS has the most rapid onset of symptoms from the time of clinical diagnosis. Although there has been significant progress made in understanding the disease, we still lack effective cures or treatments. Here we introduce an adult model of ALS to characterize the progression of synaptic deficits that precede motor neuron loss. Using a tissue specific-Gal4 and the temperature sensitive Gal80 to express human and mutant fused in sarcoma (FUS), a gene responsible for a genetic form of ALS, in the flight motor neurons in a spatial and temporally controlled manner. Synaptic deficits are characterized using the flight behavioral assay as a direct read out of flight motor neuron function. We found that overexpression of mutant FUS demonstrates a progressive loss of flight ability. We further define these synaptic defects using synaptic markers to understand how and when neuromuscular junctions (NMJs) are impaired before motor neuron loss. We also characterize the adult ventral abdominal NMJs in the same manner using a motor neuron driver specific to these NMJs. With this model, we hope to elucidate the mechanisms that underly synapse loss in a structural and functional manner.

Characterizing synaptic deficits at adult neuromuscular Junctions in a model of Amyotrophic Lateral Sclerosis