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Publication : Estrogen signaling in the ventromedial hypothalamus is required for the development of aggression circuitry in male mice.

First Author  Zha X Year  2025
Journal  Curr Biol Volume  35
Issue  11 Pages  2684-2696.e6
PubMed ID  40403719 Mgi Jnum  J:368634
Mgi Id  MGI:8216960 Doi  10.1016/j.cub.2025.04.076
Citation  Zha X, et al. (2025) Estrogen signaling in the ventromedial hypothalamus is required for the development of aggression circuitry in male mice. Curr Biol 35(11):2684-2696.e6
abstractText  Aggression in male mice depends on developmental estrogen exposure, yet the neural mechanisms underlying this phenomenon remain poorly understood. Although estrogen receptor alpha (Esr1) has served as a genetic marker to identify aggression-regulating neurons in the ventrolateral division of ventromedial hypothalamus (VMHvl), its functional role in organizing male-aggression circuits remains poorly understood. Here, we developed a genetic strategy to knock out Esr1 in VMHvl neurons while simultaneous tracing and manipulating Esr1-deleted cells. Developmental Esr1 knockout selectively altered synaptic inputs from aggression-regulating regions onto VMHvl neurons, with a stronger effect observed in males, revealing the posterior intralaminar thalamic nucleus (PIL) as a critical upstream region involved in male aggression. Additionally, VMHvl Esr1+ neurons in knockout males showed reduced excitability and failed to initiate attacks upon chemogenetic activation. These findings underscore the essential role of Esr1 in establishing male-specific aggression circuits, providing new insights into male-specific neural circuit development and function.
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