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Cortical synapses of the world’s smallest mammal: an FIB/SEM study in the Etruscan shrew

The main aim of the present study was to determine if synapses from the exceptionally small brain of the Etruscan shrew show any peculiarities compared to the much larger human brain. This study constitutes the first description of the Etruscan shrew synaptic characteristics using Focused Ion Beam/Scanning Electron Microscopy (FIB/SEM). We analyzed the synaptic density and a variety of structural characteristics of 7,239 3D reconstructed synapses, obtaining the following major results: (i) cortical synaptic density was very high, particularly in layer I; (ii) the vast majority of synapses were excitatory, with the highest proportion found in layer I; (iii) excitatory synapses were larger than inhibitory synapses in all layers except in layer VI; and (iv) synapses were either randomly distributed in space or showed a slight tendency to be organised in a regular arrangement. Some of these general synaptic characteristics are remarkably similar to those found in the human cerebral cortex. However, the cortical volume of the human brain is about 50,000 times larger than the cortical volume of the Etruscan shrew, while the total number of cortical synapses in human is only 20,000 times the number of synapses in the shrew, and synaptic junctions are 35% smaller in the Etruscan shrew. Thus, the differences in the number and size of synapses cannot be attributed to a brain size scaling effect but rather to adaptations of synaptic circuits to particular functions. The present work provides a quantitative dataset from the Etruscan shrew synapses — not only contributing to the knowledge of the ultrastructure of the mammalian cortex, but also identifying common and differing principles of synaptic organization.