F. Kawasaki et Rw. Ordway, The Drosophila NSF protein, dNSF1, plays a similar role at neuromuscular and some central synapses, J NEUROPHYS, 82(1), 1999, pp. 123-130
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.