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Abstract

The mammalian neocortex carries out complex mental processes such as cognition, perception and decision-making through the interactions of billions of neurons connected by trillions of synapses. We are just beginning to understand how networks of neurons become wired together during development to give rise to cortical computations. Recent studies have shown that excitatory cortical neurons with a shared ontogenetic lineage form vertical columns spanning multiple cortical layers and that these “sister cells” are more likely to be synaptically connected to each other than to nearby, unrelated neurons. However, the precise wiring diagram between sister cells is unknown. Here we show that connectivity between sister cells depends on the laminar position of the pre- and post-synaptic neurons. In contrast to previous studies, we find that although sister cells residing in different cortical layers are more likely to be connected, sister cells located within the same layer are less likely to be connected to each other compared to distance-matched controls. Avoidance of cells that receive common input may be a fundamental principle of information processing within a cortical column. Our findings challenge the prevailing hypothesis that shared developmental lineage is always associated with an increase in connectivity, and suggest that both attraction and repulsion play an important role in shaping cortical circuits.