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 synaptic input to cells projecting back to the input source (looped neurons) with neighboring 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 excitatory connections with looped neurons versus non-looped neurons in layer (L) 5 and L6, but not in L2/3. In most cases, these stronger connections in looped L5 neurons were located on their apical tufts, but not on their perisomatic dendrites. Our results reveal that cortico-cortical connections are selectively wired to form monosynaptic excitatory loops and support a differential role of supragranular and subgranular neurons in hierarchical recurrent computations.