Ultrastructural Analysis of Hippocampal Neuropil from the Connectomics Perspective

SummaryComplete reconstructions of vertebrate neuronal circuits on the synaptic level require new approaches. Here, serial section transmission electron microscopy was automated to densely reconstruct four volumes, totaling 670 μm3, from the rat hippocampus as proving grounds to determine when axo-dendritic proximities predict synapses. First, in contrast with Peters' rule, the density of axons within reach of dendritic spines did not predict synaptic density along dendrites because the fraction of axons making synapses was variable. Second, an axo-dendritic touch did not predict a synapse; nevertheless, the density of synapses along a hippocampal dendrite appeared to be a universal fraction, 0.2, of the density of touches. Finally, the largest touch between an axonal bouton and spine indicated the site of actual synapses with about 80% precision but would miss about half of all synapses. Thus, it will be difficult to predict synaptic connectivity using data sets missing ultrastructural details that distinguish between axo-dendritic touches and bona fide synapses.

► First dense reconstruction in mammalian brain at a few-nanometer (synapse) resolution
► Peters' rule does not reliably predict the density of synapses along dendrites
► A dendrite's touches with axons predict the density but not individual synapses
► Axonal and dendritic geometries alone are insufficient for circuit reconstruction