title: Combinatorial effects of odorants on mouse behavior.
abstract: The mechanisms by which odors induce instinctive behaviors are largely unknown. Odor detection in the mouse nose is mediated by >1, 000 different odorant receptors (ORs) and trace amine-associated receptors (TAARs). Odor perceptions are encoded combinatorially by ORs and can be altered by slight changes in the combination of activated receptors. However, the stereotyped nature of instinctive odor responses suggests the involvement of specific receptors and genetically programmed neural circuits relatively immune to extraneous odor stimuli and receptor inputs. Here, we report that, contrary to expectation, innate odor-induced behaviors can be context-dependent. First, different ligands for a given TAAR can vary in behavioral effect. Second, when combined, some attractive and aversive odorants neutralize one another's behavioral effects. Both a TAAR ligand and a common odorant block aversion to a predator odor, indicating that this ability is not unique to TAARs and can extend to an aversive response of potential importance to survival. In vitro testing of single receptors with binary odorant mixtures indicates that behavioral blocking can occur without receptor antagonism in the nose. Moreover, genetic ablation of a single receptor prevents its cognate ligand from blocking predator odor aversion, indicating that the blocking requires sensory input from the receptor. Together, these findings indicate that innate odor-induced behaviors can depend on context, that signals from a single receptor can block innate odor aversion, and that instinctive behavioral responses to odors can be modulated by interactions in the brain among signals derived from different receptors.
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Saraiva
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Kunio
authors.initials: K
authors.lastname: Kondoh
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Ye
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Kyoung-Hye
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 lbuck@fhcrc.org.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Buck
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009812:Odorants; D055696:Olfactory Perception / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D018035:Receptors, Odorant / Q000502:physiology*; D015398:Signal Transduction; D012903:Smell / Q000502:physiology; D000095383:Trace Amine-Associated Receptors
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D018035:Receptors, Odorant; C582062:TAAR5 protein, mouse; D000095383:Trace Amine-Associated Receptors
keywords: TAAR; behavior; odorants; olfaction