Antimicrobial peptides modulate long-term memory

Antimicrobial peptides act as a host defense mechanism and regulate the commensal microbiome. To obtain a comprehensive view of genes contributing to long-term memory we performed mRNA sequencing from single Drosophila heads following behavioral training that produces long-lasting memory. Surprisingly, we find that two immune peptides with antimicrobial activity, Diptericin B and Gram-Negative Bacteria Binding Protein like 3, regulate long-term but not short-term memory or instinctive behavior in Drosophila. The cellular requirement of these two peptides is distinct: head fat body for DptB, and neurons for GNBP-like3. That antimicrobial peptides influence memory provides a novel example of the emerging link between the immune and nervous systems and reveals that some immune peptides may have been repurposed in the nervous system.