Laminar-specific cortico-cortical loops in mouse visual cortex

Many theories propose recurrent interactions across the cortical hierarchy, but it is unclear if cortical circuits are selectively wired to implement looped computations. Using subcellular channelrhodopsin-2-assisted circuit mapping in mouse visual cortex, we compared feedforward (FF) or feedback (FB) cortico-cortical input to cells projecting back to the input source (looped neurons) with cells projecting to a different cortical or subcortical area (non-looped neurons). Despite having different laminar innervation patterns, FF and FB afferents showed similar cell-type selectivity, making stronger connections with looped neurons versus non-looped neurons in layer (L) 5 and L6, but not in L2/3. FB inputs preferentially innervated the apical tufts of looped L5 neurons, but not their perisomatic dendrites. Our results reveal that interareal cortical connections are selectively wired into monosynaptic excitatory loops involving L6 and the apical dendrites of L5 neurons, supporting a role of these circuit elements in hierarchical recurrent computations.