Prior experience establishes a proactive cortical filter that blocks redundant associations

Prior experience allows selective learning by filtering out redundant cues, as exemplified by blocking, in which prior learning about one cue prevents a novel but redundant cue from being learned during subsequent compound conditioning. Top-down cortico-cortical pathways have been implicated in sensory filtering, but whether, how, and when they contribute to blocking remain unknown. Here we establish a head-fixed blocking paradigm in mice in which prior auditory cue-reward learning prevents a redundant somatosensory cue-reward association during subsequent compound conditioning. We found that a projection from anterior cingulate cortex (ACC) to primary somatosensory cortex (S1) facilitates blocking. Prior auditory learning establishes ACC-driven inhibitory control over S1 via parvalbumin neurons, before explicit somatosensory experience, thereby suppressing burst responses to the somatosensory cue, limiting network plasticity, and promoting blocking. These findings propose a proactive cortical filter that preconfigures inhibitory sensory bias to constrain future learning about redundant cues. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/736748v1_ufig1.gif" ALT="Figure 1"> View larger version (63K): org.highwire.dtl.DTLVardef@1882ef3org.highwire.dtl.DTLVardef@1c268d2org.highwire.dtl.DTLVardef@6fc96forg.highwire.dtl.DTLVardef@111cbfa_HPS_FORMAT_FIGEXP M_FIG C_FIG