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Biology subjects

Atsumi, Y.

Publications and source records attributed to Atsumi, Y..

2 recordsLinked to original sources

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@6e1c4org.highwire.dtl.DTLVardef@1d01b49org.highwire.dtl.DTLVardef@1af67fdorg.highwire.dtl.DTLVardef@d42d8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Enhanced anti-tumor effects through continuous administration of engineered CAR-macrophages derived from pluripotent stem cell-derived myeloid celllines.

Even after chimeric antigen receptor (CAR)-based immunotherapy has dramatically changed therapeutic approaches for malignancies, balancing therapeutic efficacy with labor and financial cost remains a major problem for immunotherapy. Current study developed a cost-effective and enhanced approach to chimeric antigen receptor (CAR)-macrophage therapy for cancer and demonstrated its therapeutic effects by repeated administration of anti-HER2 CAR macrophages generated from human pluripotent stem cell (PSC)-derived immortalized myeloid cell lines (ML). These ML-derived CAR macrophages (CAR-ML-MPs) exhibit potent antigen-specific killing activity against HER2-expressing tumor cells by phagocytosis in vitro and effectively inhibit tumor progression in vivo, which is enhanced by repeated administration. CAR-ML-MPs provide a promising off-the-shelf cellular resource for tumor adoptive cell immunotherapy, solving the cost and time problems associated with conventional CAR-based immunotherapy.

bioengineering↗