title: Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice.
abstract: Most mammals have two major olfactory subsystems: the main olfactory system (MOS) and vomeronasal system (VNS). It is now widely accepted that the range of pheromones that control social behaviors are processed by both the VNS and the MOS. However, the functional contributions of each subsystem in social behavior remain unclear. To genetically dissociate the MOS and VNS functions, we established two conditional knockout mouse lines that led to either loss-of-function in the entire MOS or in the dorsal MOS. Mice with whole-MOS loss-of-function displayed severe defects in active sniffing and poor survival through the neonatal period. In contrast, when loss-of-function was confined to the dorsal MOB, sniffing behavior, pheromone recognition, and VNS activity were maintained. However, defects in a wide spectrum of social behaviors were observed: attraction to female urine and the accompanying ultrasonic vocalizations, chemoinvestigatory preference, aggression, maternal behaviors, and risk-assessment behaviors in response to an alarm pheromone. Functional dissociation of pheromone detection and pheromonal induction of behaviors showed the anterior olfactory nucleus (AON)-regulated social behaviors downstream from the MOS. Lesion analysis and neural activation mapping showed pheromonal activation in multiple amygdaloid and hypothalamic nuclei, important regions for the expression of social behavior, was dependent on MOS and AON functions. Identification of the MOS-AON-mediated pheromone pathway may provide insights into pheromone signaling in animals that do not possess a functional VNS, including humans.
authors.affiliation: Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan;
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Matsuo
authors.affiliation: Companion-Animal Research, School of Veterinary Medicine, Azabu University, Kanagawa 229-8501, Japan;
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Companion-Animal Research, School of Veterinary Medicine, Azabu University, Kanagawa 229-8501, Japan;
authors.forename: Akari
authors.initials: A
authors.lastname: Asaba
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan; Department of Cell Science, Institutes for Biomedical Sciences, School of Medicine, Fukushima Medical University, Fukushima 960-1295, Japan;
authors.forename: Naokazu
authors.initials: N
authors.lastname: Inoue
authors.affiliation: Department of Chemistry and Biochemistry, Waseda University, Tokyo 169-8555, Japan; and.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kanomata
authors.affiliation: Companion-Animal Research, School of Veterinary Medicine, Azabu University, Kanagawa 229-8501, Japan;
authors.forename: Takefumi
authors.initials: T
authors.lastname: Kikusui
authors.affiliation: Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan; reiko@obi.or.jp kobayakawa@obi.or.jp.
authors.forename: Reiko
authors.initials: R
authors.lastname: Kobayakawa
authors.affiliation: Department of Functional Neuroscience, Osaka Bioscience Institute, Osaka 565-0874, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan reiko@obi.or.jp kobayakawa@obi.or.jp.
authors.forename: Ko
authors.initials: K
authors.lastname: Kobayakawa
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010675:Pheromones / Q000502:physiology*; D012903:Smell / Q000502:physiology*; D012919:Social Behavior
chemical_list: D010675:Pheromones
keywords: main olfactory system; pheromone processing; social behavior; vomeronasal system