Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles

Elife. 2016 Aug 18:5:e18167. doi: 10.7554/eLife.18167.


Classic theories link cognitive abilities to synaptic properties and human-specific biophysical features of synapses might contribute to the unparalleled performance of the human cerebral cortex. Paired recordings and multiple probability fluctuation analysis revealed similar quantal sizes, but 4-times more functional release sites in human pyramidal cell to fast-spiking interneuron connections compared to rats. These connections were mediated on average by three synaptic contacts in both species. Each presynaptic active zone (AZ) contains 6.2 release sites in human, but only 1.6 in rats. Electron microscopy (EM) and EM tomography showed that an AZ harbors 4 docked vesicles in human, but only a single one in rats. Consequently, a Katz's functional release site occupies ~0.012 μm(2) in the human presynaptic AZ and ~0.025 μm(2) in the rat. Our results reveal a robust difference in the biophysical properties of a well-defined synaptic connection of the cortical microcircuit of human and rodents.

Keywords: EPSC; cerebral cortex; human; interneuron; neuroscience; quantal analysis; rat; release site.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysical Phenomena
  • Electron Microscope Tomography
  • Humans
  • Interneurons / physiology*
  • Microscopy, Electron, Transmission
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Pyramidal Cells / physiology*
  • Rats
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure