Scalable control of mounting and attack by Esr1+ neurons in the ventromedial hypothalamus
Open accessAbstract
Social behaviours, such as aggression or mating, proceed through a series of appetitive and consummatory phases that are associated with increasing levels of arousal. How such escalation is encoded in the brain, and linked to behavioural action selection, remains an unsolved problem in neuroscience. The ventrolateral subdivision of the murine ventromedial hypothalamus (VMHvl) contains neurons whose activity increases during male-male and male-female social encounters. Non-cell-type-specific optogenetic activation of this region elicited attack behaviour, but not mounting. We have identified a subset of VMHvl neurons marked by the oestrogen receptor 1 (Esr1), and investigated their role in male social behaviour. Optogenetic manipulations indicated that Esr1(+) (but not Esr1(-)) neurons are sufficient to initiate attack, and that their activity is continuously required during ongoing agonistic behaviour. Surprisingly, weaker optogenetic activation of these neurons promoted mounting behaviour, rather than attack, towards both males and females, as well as sniffing and close investigation. Increasing photostimulation intensity could promote a transition from close investigation and mounting to attack, within a single social encounter. Importantly, time-resolved optogenetic inhibition experiments revealed requirements for Esr1(+) neurons in both the appetitive (investigative) and the consummatory phases of social interactions. Combined optogenetic activation and calcium imaging experiments in vitro, as well as c-Fos analysis in vivo, indicated that increasing photostimulation intensity increases both the number of active neurons and the average level of activity per neuron. These data suggest that Esr1(+) neurons in VMHvl control the progression of a social encounter from its appetitive through its consummatory phases, in a scalable manner that reflects the number or type of active neurons in the population.
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Anogenital sniffing and attack behavior have been shown to be regulated by a common neuronal population.
“Additionally, anogenital sniffing and attack behavior have been shown to be regulated by a common neuronal population”
From Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors (2020) · cites this paper as Lee et al., 2014
Nicotine might act to scale social and agonistic behavior.
“suggesting that nicotine might act to scale social and agonistic behavior (Driscoll and Baettig, 1981) shifting the curve in a similar way as does increasing the activity of a subset of neurons in the mouse ventromedial hypothalamus (Lee et al., 2014)”
From Mood and anxiety regulation by nicotinic acetylcholine receptors: A potential pathway to modulate aggression and related behavioral states (2015) · cites this paper as Lee et al., 2014
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- Authors
- Lee, H., Kim, D.-W., Remedios, R., Anthony, T. E., Chang, A., Madisen, L., Zeng, H., & Anderson, D. J.
- Affiliations
- California Institute of Technology (US)
- Allen Institute for Brain Science (US)
- Corresponding author
- Anderson, David J.
- Venue
- Nature
- Published
- 2014-04-16
- Volume
- 509
- Issue
- 7502
- Pages
- 627-632
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4098836
- OpenAlex
- W2065679484
- Cited by
- 479
- References
- 35
- Citations by year
- 2026: 29 · 2025: 41 · 2024: 44 · 2023: 51 · 2022: 49 · 2021: 34 · 2020: 42 · 2019: 32 · 2018: 56 · 2017: 30 · 2016: 34 · 2015: 28 · 2014: 8
- FWCI
- 49.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (1f32hd055198-01)
- National Institute of Mental Health (R01MH085082, R01MH070053)
- National Institute of Neurological Disorders and Stroke (K99NS074077)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (F32 HD055198, 1F32HD055198-01)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- ventromedial hypothalamus, mounting behavior, social investigation, optogenetic stimulation, calcium imaging, c-fos
- MeSH terms
- Aggression, Animals, Female, Male, Neurons, Sexual Behavior, Animal, Ventromedial Hypothalamic Nucleus, Integrases, Estrogen Receptor alpha, Mice, Optogenetics
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