{1554} revision 0 modified: 10-12-2021 17:03 gmt

Ultrastructural readout of in vivo synaptic activity for functional connectomics

  • Anna Simon, Arnd Roth, Arlo Sheridan, Mehmet Fişek, Vincenzo Marra, Claudia Racca, View ORCID ProfileJan Funke, View ORCID ProfileKevin Staras, Michael Häusser
  • Did FIB-SEM on FM1-43 dye labeled synapses, then segmented the cells using machine learning, as Jan has pioneered.
    • FM1-43FX is membrane impermeable, and labels only synaptic vesicles that have been recycled after dye loading. (Invented in 1992!)
    • FM1-43FX is also able to photoconvert diaminobenzidene (DAB) into a amorphous highly conjugated polymer with high affinity for osmium tetroxide
  • This allows for a snapshot of ultrastructural presynaptic plasticity / activity.
  • N=84 boutons, but n=7 pairs / triples of boutons from the same axon.
    • These boutons have the same presynaptic spiking activity, and hence are expected to have the same release probability, and hence the same photoconversion (PC) labeling.
      • But they don't! The ratio of PC+ vesicle numbers between boutons on the same neuron is low, mean < 0.4, which suggests some boutons have high neurotransmitter release and recycling, others have low...
  • Quote in the abstract: We also demonstrate that neighboring boutons of the same axon, which share the same spiking activity, can differ greatly in their presynaptic release probability.
    • Well, sorta, the data here is a bit weak. It might all be lognormal fluctuations, as has been well demonstrated.
    • When I read it I was excited to think of the influence of presynaptic inhibition / modulation, which has not been measured here, but is likely to be important.