We describe automated technologies to probe the structure of neural tissue at nanometer resolution and use them to generate a saturated reconstruction of a sub-volume of mouse neocortex in which all cellular objects (axons, dendrites, and glia) and many sub-cellular components (synapses, synaptic vesicles, spines, spine apparati, postsynaptic densities, and mitochondria) are rendered and itemized in a database. We explore these data to study physical properties of brain tissue. For example, by tracing the trajectories of all excitatory axons and noting their juxtapositions, both synaptic and non-synaptic, with every dendritic spine we refute the idea that physical proximity is sufficient to predict synaptic connectivity (the so-called Peters' rule). This online minable database provides general access to the intrinsic complexity of the neocortex and enables further data-driven inquiries.

Associating stimuli with positive or negative reinforcement is essential for survival, but a complete wiring diagram of a higher-order circuit supporting associative memory has not been previously available. Here we reconstruct one such circuit at synaptic resolution, the Drosophila larval mushroom body. We find that most Kenyon cells integrate random combinations of inputs but that a subset receives stereotyped inputs from single projection neurons. This organization maximizes performance of a model output neuron on a stimulus discrimination task. We also report a novel canonical circuit in each mushroom body compartment with previously unidentified connections: reciprocal Kenyon cell to modulatory neuron connections, modulatory neuron to output neuron connections, and a surprisingly high number of recurrent connections between Kenyon cells. Stereotyped connections found between output neurons could enhance the selection of learned behaviours. The complete circuit map of the mushroom body should guide future functional studies of this learning and memory centre.

We present a method to estimate block membership of nodes in a random graph generated by a stochastic blockmodel. We use an embedding procedure motivated by the random dot product graph model, a particular example of the latent position model. The embedding associates each node with a vector; these vectors are clustered via minimization of a square error criterion. We prove that this method is consistent for assigning nodes to blocks, as only a negligible number of nodes will be mis-assigned. We prove consistency of the method for directed and undirected graphs. The consistent block assignment makes possible consistent parameter estimation for a stochastic blockmodel. We extend the result in the setting where the number of blocks grows slowly with the number of nodes. Our method is also computationally feasible even for very large graphs. We compare our method to Laplacian spectral clustering through analysis of simulated data and a graph derived from Wikipedia documents.