Dense connectomic reconstruction in layer 4 of the somatosensory cortex

TLDR

The dense circuit structure of the mammalian cerebral cortex remains largely unknown, and although 3‑D electron microscopy now enables imaging of large neuropil volumes, dense connectome reconstruction remains the bottleneck. The authors reconstructed a ~500,000‑µm³ volume of layer 4 mouse barrel cortex, roughly 300‑fold larger than prior dense cortical reconstructions. The data revealed inhibitory and excitatory neuron subtypes that could not be inferred from geometry, quantified Hebbian‑adaptation signatures setting upper bounds on saturated LTP, and demonstrated a scalable approach for locally dense connectomic phenotyping of mammalian cortical circuitry.

Abstract

The dense circuit structure of mammalian cerebral cortex is still unknown. With developments in three-dimensional electron microscopy, the imaging of sizable volumes of neuropil has become possible, but dense reconstruction of connectomes is the limiting step. We reconstructed a volume of ~500,000 cubic micrometers from layer 4 of mouse barrel cortex, ~300 times larger than previous dense reconstructions from the mammalian cerebral cortex. The connectomic data allowed the extraction of inhibitory and excitatory neuron subtypes that were not predictable from geometric information. We quantified connectomic imprints consistent with Hebbian synaptic weight adaptation, which yielded upper bounds for the fraction of the circuit consistent with saturated long-term potentiation. These data establish an approach for the locally dense connectomic phenotyping of neuronal circuitry in the mammalian cortex.