The Drosophila NSF protein, dNSF1, plays a similar role at neuromuscular and some central synapses

The N-ethylmaleimide sensitive fusion protein (NSF) was originally identifi ed as a cytosolic factor required for constitutive vesicular transport and later implicated in synaptic vesicle trafficking as well. Our previous work at neuromuscular synapses in the temperature-sensitive NSF mutant, comatos e (comt), has shown that the comt gene product, dNSF1, functions after syna ptic vesicle docking in the priming of vesicles for fast calcium-triggered fusion. Here we investigate whether dNSF1 performs a similar function at ce ntral synapses associated with the well-characterized giant fiber neural pa thway. These include a syn apse within the giant fiber pathway, made by the peripherally synapsing interneuron (PSI), as well as synapses providing in put to the giant fiber pathway. The latency (delay) between stimulation and a resulting muscle action potential was used to assess the function of eac h class of synapses. Repetitive stimulation of the giant fiber pathway in c omt produced wild-type responses at both 20 and 36 degrees C, exhibiting a characteristic and constant latency between stimulation and the muscle resp onse. In contrast, stimulation of presynaptic inputs to the giant fiber (re ferred to as the "long latency pathway") revealed a striking difference bet ween wild type and comt at 36 degrees C. Repetitive stimulation of the long latency pathway led to a progressive, activity-dependent increase in the r esponse latency in comt, but not in wild type. Thus the giant fiber pathway , including the PSI synapse, appears to function normally in comt, whereas the presynaptic inputs to the giant fiber pathway are disrupted. Several as pects of the progressive latency increase observed in the long latency path way can be understood in the context of the activity-dependent reduction in neurotransmitter release we observed previously at neuromuscular synapses. These results suggest that repetitive stimulation causes a progressive red uction in neurotransmitter release by presynaptic inputs to the giant fiber neuron, resulting in an increased latency preceding a giant fiber action p otential. Thus synapses presynaptic to the giant fiber appear to utilize dN SF1 in a manner similar to the neuromuscular synapse, whereas the PSI chemi cal synapse may differ with respect to the expression or activity of dNSF1.