A single vomeronasal receptor promotes intermale aggression through dedicated hypothalamic neurons.

The pheromonal information received by the vomeronasal system plays a crucial role in regulating social behaviors such as aggression in mice. Despite accumulating knowledge of the brain regions involved in aggression, the specific vomeronasal receptors and the exact neural circuits responsible for pheromone-mediated aggression remain unknown. Here, we identified one murine vomeronasal receptor, Vmn2r53, that is activated by urine from males of various strains and is responsible for evoking intermale aggression. We prepared a purified pheromonal fraction and Vmn2r53 knockout mice and applied genetic tools for neuronal activity recording, manipulation, and circuit tracing to decipher the neural mechanisms underlying Vmn2r53-mediated aggression. We found that Vmn2r53-mediated aggression is regulated by specific neuronal populations in the ventral premammillary nucleus and the ventromedial hypothalamic nucleus. Together, our results shed light on the hypothalamic regulation of male aggression mediated by a single vomeronasal receptor.

• Publication year

  2022

• Venue

  Neuron

• Publication date

  2022-05-26

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.neuron.2022.05.002PMID 35654036
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Hierarchical Representations of Aggression in a Hypothalamic-Midbrain Circuit.

  2020cited by this paper
• Specific Hypothalamic Neurons Required for Sensing Conspecific Male Cues Relevant to Inter-male Aggression.

  2020cited by this paper
• Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice

  2020cited by this paper
• Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP

  2020cited by this paper
• Potentiation of Divergent Medial Amygdala Pathways Drives Experience-Dependent Aggression Escalation

  2020cited by this paper
• An open-source video tracking system for mouse locomotor activity analysis

  2020cited by this paper
• Central role of G protein Gαi2 and Gαi2+ vomeronasal neurons in balancing territorial and infant-directed aggression of male mice

  2019cited by this paper
• Identification of an Intra- and Inter-specific Tear Protein Signal in Rodents.

  2018cited by this paper
• A neural network for intermale aggression to establish social hierarchy

  2018cited by this paper
• In-vivo activation of vomeronasal neurons shows adaptive responses to pheromonal stimuli

  2018cited by this paper
• Neural coding of sex-specific social information in the mouse brain.

  2018cited by this paper
• Sexual rejection via a vomeronasal receptor-triggered limbic circuit

  2018cited by this paper
• Pronounced strain-specific chemosensory receptor gene expression in the mouse vomeronasal organ

  2017cited by this paper
• Ventromedial Hypothalamus and the Generation of Aggression

  2017cited by this paper
• A Labeled-Line Neural Circuit for Pheromone-Mediated Sexual Behaviors in Mice.

  2017cited by this paper
• Social Behaviour Shapes Hypothalamic Neural Ensemble Representations Of Conspecific Sex

  2017cited by this paper
• Social Control of Hypothalamus-Mediated Male Aggression.

  2017cited by this paper
• Exocrine Gland-Secreting Peptide 1 Is a Key Chemosensory Signal Responsible for the Bruce Effect in Mice.

  2017cited by this paper
• Circuit modules linking internal states and social behaviour in flies and mice

  2016cited by this paper
• Self-Exposure to the Male Pheromone ESP1 Enhances Male Aggressiveness in Mice.

  2016cited by this paper
• Hypothalamic control of male aggression-seeking behavior

  2016cited by this paper
• BORIS: a free, versatile open‐source event‐logging software for video/audio coding and live observations

  2016cited by this paper
• Natural neural projection dynamics underlying social behavior.

  2014cited by this paper
• Mammalian pheromones.

  2014cited by this paper
• Scalable Control of Mounting and Attack by ESR1+ Neurons in the Ventromedial Hypothalamus

  2014cited by this paper
• Representing sex in the brain, one module at a time.

  2014cited by this paper
• Genetic mapping of escalated aggression in wild-derived mouse strain MSM/Ms: association with serotonin-related genes

  2014cited by this paper
• Decoding Ventromedial Hypothalamic Neural Activity during Male Mouse Aggression

  2014cited by this paper
• Murine pheromone proteins constitute a context-dependent combinatorial code governing multiple social behaviors.

  2014cited by this paper
• Ultra-sensitive fluorescent proteins for imaging neuronal activity

  2013cited by this paper
• Dissecting local circuits: parvalbumin interneurons underlie broad feedback control of olfactory bulb output.

  2013cited by this paper
• Design and generation of recombinant rabies virus vectors

  2013cited by this paper
• Sexually dimorphic neurons in the ventromedial hypothalamus govern mating in both sexes and aggression in males.

  2013cited by this paper
• A juvenile mouse pheromone inhibits sexual behavior through the vomeronasal system

  2013cited by this paper
• Molecular profiling of activated neurons by phosphorylated ribosome capture.

  2012cited by this paper
• G protein Gαo is essential for vomeronasal function and aggressive behavior in mice

  2011cited by this paper
• Rapid, reversible activation of AgRP neurons drives feeding behavior in mice.

  2011cited by this paper
• Distribution of mRNAs encoding classical progestin receptor, progesterone membrane components 1 and 2, serpine mRNA binding protein 1, and progestin and ADIPOQ receptor family members 7 and 8 in rat forebrain.

  2011cited by this paper
• Functional identification of an aggression locus in the mouse hypothalamus

  2010cited by this paper
• The male mouse pheromone ESP1 enhances female sexual receptive behaviour through a specific vomeronasal receptor

  2010cited by this paper
• Limited variation in the major urinary proteins of laboratory mice.

  2009cited by this paper
• Species Specificity in Major Urinary Proteins by Parallel Evolution

  2008cited by this paper
• Sex- and strain-specific expression and vomeronasal activity of mouse ESP family peptides.

  2007cited by this paper
• Identification of protein pheromones that promote aggressive behaviour

  2007cited by this paper
• Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand

  2007cited by this paper
• Sex-specific peptides from exocrine glands stimulate mouse vomeronasal sensory neurons

  2005cited by this paper
• Loss of sex discrimination and male-male aggression in mice deficient for TRP2.

  2002cited by this paper
• Altered sexual and social behaviors in trp2 mutant mice

  2002cited by this paper
• Loss of Sex Discrimination and Male-Male Aggression in Mice Deficient for TRP2

  2002cited by this paper
• Individual recognition in mice mediated by major urinary proteins

  2001cited by this paper
• Projections of the ventral premammillary nucleus

  1992cited by this paper
• Synthetic pheromones that promote inter-male aggression in mice.

  1985cited by this paper
• The Nucleus Premammillaris Ventralis (PMV) and Aggressive Behavior in the Rat

  1980cited by this paper
• Pheromones and their Effect on Aggression in Mice

  1970cited by this paper

• Sexual dimorphism in pheromone perception across worms, flies, and rodents.

  2025cites this paper
• Sexually dimorphic processing of pheromonal information in mice.

  2025cites this paper
• The ventral premammillary nucleus at the interface of environmental cues and social behaviors

  2025cites this paper
• Sexual dimorphism of the ventral premammillary nucleus of the rat: stereological evaluation

  2025cites this paper
• Tex15 is required for vomeronasal sensory neuron diversity and male pheromone detection

  2025influential citation
• The neural computation of affective internal states in the hypothalamus: A dynamical systems perspective.

  2025cites this paper
• Seasonal Changes of Circulating Sex Steroid Hormones Associated With Vomeronasal Function of the Male Muskrats (Ondatra zibethicus).

  2025cites this paper
• Evolution of vertebrate olfactory receptor repertoires and their function

  2025cites this paper
• Impaired pheromone detection and abnormal sexual behavior in female mice deficient for ancV1R.

  2024cites this paper
• Estrogen Receptor Alpha–Expressing Neurons in Bed Nucleus of the Stria Terminalis and Hypothalamus Encoding Aggression and Mating

  2024cites this paper
• Molecular, Cellular, and Developmental Organization of the Mouse Vomeronasal organ at Single Cell Resolution

  2024cites this paper
• Characterization and phylogenetic analysis of vomeronasal receptors in the female muskrat (Ondatra zibethicus).

  2024cites this paper
• Hypothalamic neurons that mirror aggression

  2024cites this paper
• Molecular, cellular, and developmental organization of the mouse vomeronasal organ at single cell resolution

  2024cites this paper
• Type 2 vomeronasal receptor‐A4 subfamily: Potential predator sensors in mice

  2024cites this paper
• Neural basis for pheromone signal transduction in mice

  2024cites this paper
• Chemogenetic Excitation of Ventromedial Hypothalamic Steroidogenic Factor 1 (SF1) Neurons Increases Muscle Thermogenesis in Mice

  2024cites this paper
• A pheromone receptor in cichlid fish mediates attraction to females but inhibits male parental care.

  2024cites this paper
• Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice

  2024cites this paper
• An approximate line attractor in the hypothalamus encodes an aggressive state

  2023cites this paper
• Hypothalamic neurons that mirror aggression.

  2023cites this paper
• Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice

  2023cites this paper
• Anatomically distributed neural representations of instincts in the hypothalamus

  2023cites this paper
• Pheromone Perception in Fish: Mechanisms And Modulation by Internal Status.

  2023cites this paper
• Mating status, independent of size, influences lethal fighting in an entomopathogenic nematode

  2023cites this paper
• Non-angry Aggressive Arousal and Angriffsberietschaft: A Narrative Review of the Phenomenology and Physiology of Proactive/Offensive Aggression Motivation and Escalation in People and Other Animals.

  2023cites this paper