A hypothalamic pathway that suppresses aggression toward superior opponents
authors: Dongyu Wei, Takuya Osakada, Zhichao Guo, Takashi Yamaguchi, Avni Varshneya, Rongzhen Yan, Yiwen Jiang, Dayu Lin
doi: 10.1038/s41593-023-01297-5
CITATION
Wei, D., Osakada, T., Guo, Z., Yamaguchi, T., Varshneya, A., Yan, R., Jiang, Y., & Lin, D. (2023). A hypothalamic pathway that suppresses aggression toward superior opponents. Nature Neuroscience, 26(5), 774–787. https://doi.org/10.1038/s41593-023-01297-5
ABSTRACT
Aggression is costly and requires tight regulation. Here we identify the projection from estrogen receptor alpha-expressing cells in the caudal part of the medial preoptic area (cMPOAEsr1) to the ventrolateral part of the ventromedial hypothalamus (VMHvl) as an essential pathway for modulating aggression in male mice. cMPOAEsr1 cells increase activity mainly during male–male interaction, which differs from the female-biased response pattern of rostral MPOAEsr1 (rMPOAEsr1) cells. Notably, cMPOAEsr1 cell responses to male opponents correlated with the opponents’ fighting capability, which mice could estimate based on physical traits or learn through physical combats. Inactivating the cMPOAEsr1–VMHvl pathway increased aggression, whereas activating the pathway suppressed natural intermale aggression. Thus, cMPOAEsr1 is a key population for encoding opponents’ fighting capability—information that could be used to prevent animals from engaging i n disadvantageous conflicts with superior opponents by suppressing the activity of VMHvl cells essential for attack behaviors.
fleeting notes
- projection from estrogen receptor alpha expressing cells in the caudal part of the medial preoptic area (cMPOA esr1) to the ventrolateral part of the ventromedial hypothalamus (vMHvl)
- modulates aggression in male mice
- cMPOA cells increase activity during male-male interactions corresponding to the opponents fighting capabilities, estimated based on physical traits or through previous physical combats
- inactivating the cMPOA-VMHvl increases aggression
- activating pathway suppresses aggression
- cMPOA encodes opponents fighting capability by suppressing VMHv1 cells needed for attack behaviors
Methods:
- fiber photometry, using gCamp6f
- how did they classify behavior?
- DREADS - not cMPOA specific…
- anterograde virus tracing
male MPOA displays heterogenous activity during male social behaviors
- defeated animals have increased cMPOA response when reintroduced to cupped aggressor male
- activity is plastic
- RHP - measure of the ability of an animal to win a fight
- assessed based on physical characteristics, and through physical combats
- to test whether cMPOA carries RHP information they recorded cells in response to 3 different animals. a nonaggressive male, a male with similar social experience, and an aggressive male
male cMPOA activity represents social fear
cMPOA modulates male aggression
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inhibition increases attack duration and decreases attack latency towards male and female intruders
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activation almost entirely removed attack towards males
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anterograde tracing from cMPOA and found VMHvl connections and tuberal nucleus cells
- most of the MPOA to VMHvl is gabaergic and thus inhibits VMHvl
- TU has inhibitory effects on VMHvl so this may result in variety of effects seen in the VMHvl (double inhibition)
- but the glutamatergic output from MPOA activate TU more than inhibit so net effect is inhibit VMHvl
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activating the cMPOA-VMHvl circuit suppresses aggression, but increases investigation