SummaryThe thalamus receives sensory input from different circuits in the periphery. How these sensory channels are integrated at the level of single thalamic cells is not well understood. We performed targeted single-cell-initiated transsynaptic tracing to label the retinal ganglion cells that provide input to individual principal cells in the mouse lateral geniculate nucleus (LGN). We identified three modes of sensory integration by single LGN cells. In the first, 1–5 ganglion cells of mostly the same type converged from one eye, indicating a relay mode. In the second, 6–36 ganglion cells of different types converged from one eye, revealing a combination mode. In the third, up to 91 ganglion cells converged from both eyes, revealing a binocular combination mode in which functionally specialized ipsilateral inputs joined broadly distributed contralateral inputs. Thus, the LGN employs at least three modes of visual input integration, each exhibiting different degrees of specialization.

The dense reconstruction of neuronal circuits from volumetric electron microscopy (EM) data has the potential to uncover fundamental structure-function relationships in the brain. To address bottlenecks in the workflow of this emerging methodology, we developed a procedure for conductive sample embedding and a pipeline for neuron reconstruction. We reconstructed ∼98% of all neurons (>1,000) in the olfactory bulb of a zebrafish larva with high accuracy and annotated all synapses on subsets of neurons representing different types. The organization of the larval olfactory bulb showed marked differences from that of the adult but similarities to that of the insect antennal lobe. Interneurons comprised multiple types but granule cells were rare. Interglomerular projections of interneurons were complex and bidirectional. Projections were not random but biased toward glomerular groups receiving input from common types of sensory neurons. Hence, the interneuron network in the olfactory bulb exhibits a specific topological organization that is governed by glomerular identity.

Neuronal computations underlying higher brain functions depend on synaptic interactions among specific neurons. A mechanistic understanding of such computations requires wiring diagrams of neuronal networks. We examined how the olfactory bulb (OB) performs 'whitening', a fundamental computation that decorrelates activity patterns and supports their classification by memory networks. We measured odor-evoked activity in the OB of a zebrafish larva and subsequently reconstructed the complete wiring diagram by volumetric electron microscopy. The resulting functional connectome revealed an overrepresentation of multisynaptic connectivity motifs that mediate reciprocal inhibition between neurons with similar tuning. This connectivity suppressed redundant responses and was necessary and sufficient to reproduce whitening in simulations. Whitening of odor representations is therefore mediated by higher-order structure in the wiring diagram that is adapted to natural input patterns. Neuronal activity patterns evoked by natural stimuli are transformed in the brain to extract relevant information. At early processing stages, activity patterns often contain correlations Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: