RoboEM: automated 3D flight tracing for synaptic-resolution connectomics.

Mapping neuronal networks from three-dimensional electron microscopy (3D-EM) data still poses substantial reconstruction challenges, in particular for thin axons. Currently available automated image segmentation methods require manual proofreading for many types of connectomic analysis. Here we introduce RoboEM, an artificial intelligence-based self-steering 3D 'flight' system trained to navigate along neurites using only 3D-EM data as input. Applied to 3D-EM data from mouse and human cortex, RoboEM substantially improves automated state-of-the-art segmentations and can replace manual proofreading for more complex connectomic analysis problems, yielding computational annotation cost for cortical connectomes about 400-fold lower than the cost of manual error correction.

Structure and function of the hippocampal CA3 module.

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval.

Connectomic comparison of mouse and human cortex.

The human cerebral cortex houses 1000 times more neurons than that of the cerebral cortex of a mouse, but the possible differences in synaptic circuits between these species are still poorly understood. We used three-dimensional electron microscopy of mouse, macaque, and human cortical samples to study their cell type composition and synaptic circuit architecture. The 2.5-fold increase in interneurons in humans compared with mice was compensated by a change in axonal connection probabilities and therefore did not yield a commensurate increase in inhibitory-versus-excitatory synaptic input balance on human pyramidal cells. Rather, increased inhibition created an expanded interneuron-to-interneuron network, driven by an expansion of interneuron-targeting interneuron types and an increase in their synaptic selectivity for interneuron innervation. These constitute key neuronal network alterations in the human cortex.