SUMMARYActive 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.

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Social behaviors are among the most important and rewarding motivational behaviors. How dopamine, a "reward" signal, releases in the nucleus accumbens (NAc) during social behaviors has become a topic of interest for decades. However, limitations in early recording methods, such as microdialysis, prevented a complete understanding of moment-to-moment dopamine responses during social behaviors. Here, we employ a genetically encoded dopamine sensor, GRABDA2h, to record dopamine activity in the NAc core in mice and find acute changes in extracellular dopamine levels during all three phases of social behaviors: approach, investigation and consummation. Dopamine release during approach phase correlates with animal's motivation towards the conspecific whereas its release during consummatory phase signals the valence of the experience. Furthermore, dopamine release during sexual and aggressive behaviors shows sex differences that correlate with the potential value of those experiences. Overall, our results reveal rich and temporally precise motivation and value information encoded by NAc dopamine during social behaviors and beyond.