Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice

Tomohiko Matsuo, Tatsuya Hattori, Akari Asaba, Naokazu Inoue, Nobuhiro Kanomata, Takefumi Kikusui, Reiko Kobayakaw, Ko Kobayakaw

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)E311-E320
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
Publication statusPublished - 2015 Jan 20


  • Main olfactory system
  • Pheromone processing
  • Social behavior
  • Vomeronasal system

ASJC Scopus subject areas

  • General


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