Olfactory imprinting is triggered by MHC peptide ligands.

Olfactory imprinting on environmental, population- and kin-specific cues is a specific form of life-long memory promoting homing of salmon to their natal rivers and the return of coral reef fish to natal sites. Despite its ecological significance, natural chemicals for olfactory imprinting have not been identified yet. Here, we show that MHC peptides function as chemical signals for olfactory imprinting in zebrafish. We found that MHC peptides consisting of nine amino acids elicit olfactory imprinting and subsequent kin recognition depending on the MHC genotype of the fish. In vivo calcium imaging shows that some olfactory bulb neurons are highly sensitive to MHC peptides with a detection threshold at 1 pM or lower, indicating that MHC peptides are potent olfactory stimuli. Responses to MHC peptides overlapped spatially with responses to kin odour but not food odour, consistent with the hypothesis that MHC peptides are natural signals for olfactory imprinting.