Whole-brain serial-section electron microscopy in larval zebrafish.

High-resolution serial-section electron microscopy (ssEM) makes it possible to investigate the dense meshwork of axons, dendrites, and synapses that form neuronal circuits. However, the imaging scale required to comprehensively reconstruct these structures is more than ten orders of magnitude smaller than the spatial extents occupied by networks of interconnected neurons, some of which span nearly the entire brain. Difficulties in generating and handling data for large volumes at nanoscale resolution have thus restricted vertebrate studies to fragments of circuits.

The Fuzzy Logic of Network Connectivity in Mouse Visual Thalamus.

In an attempt to chart parallel sensory streams passing through the visual thalamus, we acquired a 100-trillion-voxel electron microscopy (EM) dataset and identified cohorts of retinal ganglion cell axons (RGCs) that innervated each of a diverse group of postsynaptic thalamocortical neurons (TCs). Tracing branches of these axons revealed the set of TCs innervated by each RGC cohort. Instead of finding separate sensory pathways, we found a single large network that could not be easily subdivided because individual RGCs innervated different kinds of TCs and different kinds of RGCs co-innervated individual TCs.