PT  - JOURNAL ARTICLE
AU  - Alessandro Motta
AU  - Manuel Berning
AU  - Kevin M. Boergens
AU  - Benedikt Staffler
AU  - Marcel Beining
AU  - Sahil Loomba
AU  - Christian Schramm
AU  - Philipp Hennig
AU  - Heiko Wissler
AU  - Moritz Helmstaedter
TI  - Dense connectomic reconstruction in layer 4 of the somatosensory cortex
AID  - 10.1101/460618
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 460618
4099  - http://biorxiv.org/content/early/2018/11/03/460618.short
4100  - http://biorxiv.org/content/early/2018/11/03/460618.full
AB  - The dense circuit structure of the mammalian cerebral cortex is still unknown. With developments in 3-dimensional (3D) electron microscopy, the imaging of sizeable volumes of neuropil has become possible, but dense reconstruction of connectomes from such image data is the limiting step. Here, we report the dense reconstruction of a volume of about 500,000 μm3 from layer 4 of mouse barrel cortex, about 300 times larger than previous dense reconstructions from the mammalian cerebral cortex. Using a novel reconstruction technique, FocusEM, we were able to reconstruct a total of 0.9 meters of dendrites and about 1.8 meters of axons investing only about 4,000 human work hours, about 10-25 times more efficient than previous dense circuit reconstructions. We find that connectomic data alone allows the definition of inhibitory axon types that show established principles of synaptic specificity for subcellular postsynaptic compartments. We find that also a fraction of excitatory axons exhibit such subcellular target specificity. Only about 35% of inhibitory and 55% of excitatory synaptic subcellular innervation can be predicted from the geometrical availability of membrane surface, revoking coarser models of random wiring for synaptic connections in cortical layer 4. We furthermore find evidence for enhanced variability of synaptic input composition between neurons at the level of primary dendrites in cortical layer 4. Finally, we obtain evidence for Hebbian synaptic weight adaptation in at least 24% of connections; at least 35% of connections show no sign of such previous plasticity. Together, these results establish an approach to connectomic phenotyping of local dense neuronal circuitry in the mammalian cortex.