Synaptic transmission from a neuron to its target cells occurs via neurotransmitter release from dozens to thousands of presynaptic release sites whose strength and plasticity can vary considerably. We report an in vivo imaging method that monitors real-time synaptic transmission simultaneously at many release sites with quantal resolution. We applied this method to the model glutamatergic system of the Drosophila melanogaster larval neuromuscular junction. We find that, under basal conditions, about half of release sites have a very low release probability, but these are interspersed with sites with as much as a 50-fold higher probability. Paired-pulse stimulation depresses high-probability sites, facilitates low-probability sites, and recruits previously silent sites. Mutation of the small GTPase Rab3 substantially increases release probability but still leaves about half of the sites silent. Our findings suggest that basal synaptic strength and short-term plasticity are regulated at the level of release probability at individual sites.
Summary
Background
Spontaneous “miniature” transmitter release takes place at low rates at all synapses. Long thought as an unavoidable leak, spontaneous release has recently been suggested to be mediated by distinct pre- and post-synaptic molecular machineries and to have a specialized role in setting up and adjusting neuronal circuits. It remains unclear how spontaneous and evoked transmission are related at individual synapses, how they are distributed spatially when an axon makes multiple contacts with a target and whether they are commonly regulated.
Results
Electrophysiological recordings in the Drosophila larval neuromuscular junction, in the presence of the use-dependent glutamate receptor (GluR) blocker Philanthotoxin, indicated that spontaneous and evoked transmission employ distinct sets of GluRs. In vivo imaging of transmission using synaptically-targeted GCaMP3 to detect Ca2+ influx through the GluRs revealed little spatial overlap between synapses participating in spontaneous and evoked transmission. Spontaneous and evoked transmission were oppositely correlated with presynaptic levels of the protein Brp: synapses with high Brp favored evoked transmission, whereas synapses with low Brp were more active spontaneously. High frequency stimulation did not increase the overlap between evoked and spontaneous transmission, and instead decreased the rate of spontaneous release from synapses that were highly active in evoked transmission.
Conclusions
While individual synapses can participate in both evoked and spontaneous transmission, highly-active synapses show a preference for one mode of transmission. The presynaptic protein Brp promotes evoked transmission and suppresses spontaneous release. These findings suggest the existence of presynaptic mechanisms that promote synaptic specialization to either evoked or spontaneous transmission.
We present the results of an experimental study of the current-voltage characteristics in strong magnetic field (B) of disordered, superconducting, thin-films of amorphous Indium-Oxide. As the B strength is increased superconductivity degrades, until a critical field (B c ) where the system is forced into an insulating state. We show that the differential conductance measured in the insulating phase vanishes abruptly below a well-defined temperature, resulting in a clear threshold for conduction. Our results indicate that a new collective state emerges in two-dimensional superconductors at high B.
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