Summary As an essential means to resolve conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor alpha and progesterone receptor (Esr1/PR) are essential for male but not female mouse aggression. In contrast, here we show an indispensable role of VMHvlEsr1+ cells in female aggression. This population is active when females attack naturally. Inactivation of these cells reduces female aggression whereas their activation elicits attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that show differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.

Summary Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause “septal rage”, a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of the LS-mediated modulation of aggression, we examined the influence of the LS input onto the cells in/around the ventrolateral part of the ventromedial hypothalamus (VMHvl)—a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus the LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression.

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Highlights d VMHvl vGlut2 neurons target lPAG vGlut2 neurons that project polysynaptically to the jaw d Inactivating lPAG vGlut2 neurons results in aggressive actionspecific deficits d Single-unit lPAG activity is action specific and time locked to EMG-detected biting d VMHvl-lPAG projection relays male-biased signals to generate action selectivity

Total knee arthroplasty (TKA) is the most commonly performed inpatient surgical procedure within the USA and is estimated to reach 3.48 million procedures annually by 2030. As value-based care initiatives continue to focus on hospital readmission rates and patient satisfaction, it has become essential for health care providers to develop and implement a multidisciplinary approach to enhance TKA outcomes while minimizing unnecessary expenditures. Through this necessity, clinical care pathways have been developed to standardize, organize, and improve the quality and efficiency of patient care while simultaneously encouraging the collaboration among various medical care providers. Here, we review several systems based programs and specialty care practices that can be adopted into the standard orthopedic practice.

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