Distinct organization of two cortico-cortical feedback pathways

Neocortical feedback is critical for processes like attention, prediction, and learning. A mechanistic understanding of its function requires deciphering its cell-type wiring logic. Recent studies revealed a disinhibitory circuit between motor and sensory areas in mice, where feedback preferentially targets vasointestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif is a general cortico-cortical feedback organizing principle. Combining multiple simultaneous whole-cell recordings with optogenetics we found that in contrast to this wiring rule, feedback between the hierarchically organized visual areas (lateral-medial to V1) preferentially activated somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpened feed-forward excitation by eliciting a transient increase followed by a prolonged decrease in pyramidal firing rate under sustained feed-forward input. However, under feed-forward transient input, the motor-sensory feedback facilitated pyramidal cell bursting while visual feedback increased spike time precision. Our findings argue for multiple feedback motifs implementing different dynamic non-linear operations.