The logic of single-cell projections from visual cortex

Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on ‘one neuron–one target area’ mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways. Tracing of projection neuron axons from the primary visual cortex to their targets shows that these neurons often project to multiple cortical areas of the mouse brain. Studies of cortical connectivity have produced a rough diagram of how different brain areas are connected. However, the projection patterns of individual neurons and the logic behind this pattern organization are not known. Thomas Mrsic-Flogel and colleagues use anatomical tracing and DNA barcoding to elucidate the connectivity of individual neurons in the visual cortex of mice. Although some individual neurons target a single cortical area exclusively, most of them broadcast information widely to multiple targets. These findings argue against previous notions that information transfer in the cortex occurs from neurons to specific areas.