Rapid and reversible optogenetic silencing of synaptic transmission by clustering of synaptic vesicles.

Acutely silencing specific neurons informs about their functional roles in circuits and behavior. Existing optogenetic silencers include ion pumps, channels, metabotropic receptors, and tools that damage the neurotransmitter release machinery. While the former hyperpolarize the cell, alter ionic gradients or cellular biochemistry, the latter allow only slow recovery, requiring de novo synthesis. Thus, tools combining fast activation and reversibility are needed. Here, we use light-evoked homo-oligomerization of cryptochrome CRY2 to silence synaptic transmission, by clustering synaptic vesicles (SVs). We benchmark this tool, optoSynC, in Caenorhabditis elegans, zebrafish, and murine hippocampal neurons. optoSynC clusters SVs, observable by electron microscopy. Locomotion silencing occurs with tauon ~7.2 s and recovers with tauoff ~6.5 min after light-off. optoSynC can inhibit exocytosis for several hours, at very low light intensities, does not affect ion currents, biochemistry or synaptic proteins, and may further allow manipulating different SV pools and the transfer of SVs between them.

Temporal loudness weights: Primacy effects, loudness dominance and their interaction.

Loudness judgments of sounds varying in level across time show a non-uniform temporal weighting, with increased weights assigned to the beginning of the sound (primacy effect). In addition, higher weights are observed for temporal components that are higher in level than the remaining components (loudness dominance). In three experiments, sounds consisting of 100- or 475-ms Gaussian wideband noise segments with random level variations were presented and either none, the first, or a central temporal segment was amplified or attenuated. In Experiment 1, the sounds consisted of four 100-ms segments that were separated by 500-ms gaps. Previous experiments did not show a primacy effect in such a condition. In Experiment 2, four- or ten-100-ms-segment sounds without gaps between the segments were presented to examine the interaction between the primacy effect and level dominance. As expected, for the sounds with segments separated by gaps, no primacy effect was observed, but weights on amplified segments were increased and weights on attenuated segments were decreased. For the sounds with contiguous segments, a primacy effect as well as effects of relative level (similar to those in Experiment 1) were found. For attenuation, the data indicated no substantial interaction between the primacy effect and loudness dominance, whereas for amplification an interaction was present. In Experiment 3, sounds consisting of either four contiguous 100-ms or 475-ms segments, or four 100-ms segments separated by 500-ms gaps were presented. Effects of relative level were more pronounced for the contiguous sounds. Across all three experiments, the effects of relative level were more pronounced for attenuation. In addition, the effects of relative level showed a dependence on the position of the change in level, with opposite direction for attenuation compared to amplification. Some of the results are in accordance with explanations based on masking effects on auditory intensity resolution.