biostudies-literatureShen SODNI | Intelligence Advanced Research Projects ActivityNEI NIH HHSU.S. Department of Health & Human Services | NIH | National Eye InstituteNIMH NIH HHSNINDS NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Mental Health6389https://www.ebi.ac.uk/biostudies/studies/S-EPMC9613627biostudies-literatureUnknown13(1)Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase-followed by a prolonged decrease-in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.Nature communicationsDistinct organization of two cortico-cortical feedback pathways.PMC9613627R01 EY033492R01 MH120404R01 NS110767R01 MH109556D16PC00003P30EY002520R01 MH122169P30 EY002520R01EY026927Scala FFahey PKobak DZhou NSinz FTan ZJiang XFu JTolias ASShen SReimer JfalseDistinct organization of two cortico-cortical feedback pathways.Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase-followed by a prolonged decrease-in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.2022-01-01T00:00:00Z2022 Oct2025-06-01T04:06:57.824Z2025-06-01T04:06:57.824ZS-EPMC96136273630291210.1038/s41467-022-33883-9