Hypothalamic Control of Conspecific Self-Defense

Active defense against a conspecific aggressor is essential for survival. Previous studies revealed strong c-Fos expression in the ventrolateral part of the ventromedial hypothalamus (VMHvl) in defeated animals. Here, we examined the functional relevance and in vivo responses of the VMHvl during conspecific defense. We found that VMHvl cells expressing estrogen receptor α (Esr1) are acutely excited during active conspecific defense. Optogenetic inhibition of the cells compromised an animal’s ability to actively defend against an aggressor, whereas activating the cells elicited defense-like behaviors. Furthermore, the VMHvl is known for its role in aggression. In vivo recording and c-Fos mapping revealed differential organization of the defense and aggression-responsive cells in the VMHvl. Specifically, defense-activated cells are concentrated in the anterior part of the VMHvl, which preferentially targets the periaqueductal gray (PAG). Thus, our study identified an essential neural substrate for active conspecific defense and expanded the function of the VMHvl. [Display omitted] •VMHvl, especially its anterior part, is highly excited during active social defense•Inhibiting the VMHvl Esr1+ cells compromises active defense against an aggressor•Activating the anterior VMHvl Esr1+ cells elicits defense-like behaviors•Anterior and posterior VMHvl Esr1+ cells show differential projection patterns Active defense against conspecific aggressors is essential for survival, but its underlying neural substrates remain largely unknown. Through a series of in vivo recordings and functional manipulations, Wang et al. demonstrate that cells expressing estrogen receptor α in a small medial hypothalamic nucleus are essential for defense against a bully.