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 mum2 in the human presynaptic AZ and ~0.025 mum2 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.