The columnar and laminar organization of inhibitory connections to neocortical excitatory cells

The cytoarchitectonic similarities of different neocortical regions have given rise to the idea of “canonical” connectivity between excitatory neurons of different layers within a column. It is unclear whether similarly general organizational principles also exist for inhibitory neocortical circuits. Here, we delineate and compare local inhibitory-to-excitatory wiring patterns in all principal layers of primary motor (M1), somatosensory (S1), and visual cortex (V1), using genetically targeted photostimulation in a mouse knock-in line that conditionally expresses channelrhodopsin-2 in GABAergic neurons. Inhibitory inputs to excitatory neurons derive largely from the same cortical layer within a three-column diameter. However, subsets of pyramidal cells in layers 2/3 and 5B receive extensive translaminar inhibition. These neurons are prominent in V1, where they might correspond to complex cells, less numerous in barrel cortex, and absent in M1. Although inhibitory connection patterns are stereotypical, the abundance of individual motifs varies between regions and cells, potentially reflecting functional specializations.