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To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTRcells minimally respond to aggressor cues. During defeat, aVMHvlOXTRcells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTRcell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.

• A novel pre-softening HIP treatment is developed for crack-healing in LPBF René 142 alloys. • Pre-softening treatment significantly reduces dislocation density and residual stress levels. • A superior combination of strength and ductility is achieved after SHIP treatment. The generation of defects, such as cracks and pores, presents significant challenges for high-strength metals and alloys fabricated by the quick-emerging additive manufacturing technology, and subsequent post-processing treatments are often necessary before their practical applications. In this work, a novel heat treatment approach, involving a pre-softening treatment before hot isostatic pressing (HIP), is developed to facilitate the crack-healing in René 142 superalloy produced through laser powder bed fusion. Results demonstrate that René 142 alloy exhibits a propensity for severe cracking across a wide range of printing parameters, primarily in the form of solidification cracks and liquation cracks. These cracks are formed mainly due to a wide solidification range, the presence of a liquid film, and the concentration of residual stress. The pre-softening solution heat treatment significantly reduces dislocation density and residual stress levels, and the subsequent HIP together leads to a defect-free, dense structure for René 142 superalloy. Consequently, the René 142 alloy processed by the pre-softening HIP treatment achieves an excellent combination of yield strength (850 MPa), ultimate tensile strength (1227 MPa), and elongation (13.7 %), with pseudo-equiaxed grains (120–150 µm) and square γ′ precipitates (approximately 540 nm). These findings provide valuable insights for exploring crack elimination methods in other nickel-based superalloys fabricated through additive manufacturing. [Display omitted] [ABSTRACT FROM AUTHOR]

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. cMPOAEsr1cells increase activity mainly during male–male interaction, which differs from the female-biased response pattern of rostral MPOAEsr1(rMPOAEsr1) cells. Notably, cMPOAEsr1cell 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, cMPOAEsr1is a key population for encoding opponents’ fighting capability—information that could be used to prevent animals from engaging in disadvantageous conflicts with superior opponents by suppressing the activity of VMHvl cells essential for attack behaviors.

Sexual and aggressive behaviors are fundamental to animal survival and reproduction. The medial preoptic nucleus (MPN) and ventrolateral part of the ventromedial hypothalamus (VMHvl) are essential regions for male sexual and aggressive behaviors, respectively. While key inhibitory inputs to the VMHvl and MPN have been identified, the extrahypothalamic excitatory inputs essential for social behaviors remain elusive. Here we identify estrogen receptor alpha (Esr1)-expressing cells in the posterior amygdala (PA) as a main source of excitatory inputs to the hypothalamus and key mediators for mating and fighting in male mice. We find two largely distinct PA subpopulations that differ in connectivity, gene expression, in vivo responses and social behavior relevance. MPN-projecting PAEsr1+cells are activated during mating and are necessary and sufficient for male sexual behaviors, while VMHvl-projecting PAEsr1+cells are excited during intermale aggression and promote attacks. These findings place the PA as a key node in both male aggression and reproduction circuits.

Peripheral sensitization is one of the primary mechanisms underlying the pathogenesis of chronic pain. However, candidate molecules involved in peripheral sensitization remain unclear. We have shown that store-operated calcium channels (SOCs) are expressed in the dorsal root ganglion (DRG) neurons. Whether SOCs contribute to peripheral sensitization associated with chronic inflammatory pain is elusive. Here we report that global or conditional deletion of Orai1, a major component of SOCs, attenuates CFA-induced pain hypersensitivity. To further establish the role of Orai1 in inflammatory pain, we performed calcium imaging and patch clamp recordings in wild type (WT) and Orai1 knockout (KO) DRG neurons. We found that SOC entry (SOCE) and SOC currents were significantly increased in WT, but not in Orai1 KO DRG neurons from CFA- and carrageenan-injected mice. Interestingly, the Orai1 protein level in L3/4 DRGs was not altered under peripheral inflammatory conditions. To understand how Orai1 is modulated, prostaglandin E2 (PGE2) was used to sensitize DRG neurons. PGE2-induced pain hypersensitivity was significantly reduced in Orai1 KO mice. PGE2-induced potentiation of SOCE and SOC currents was absent in Orai1 KO DRG neurons. This effect was attenuated by a PGE2 receptor 1 (EP1) antagonist and mimicked by EP1 agonist. Selective inhibitors of Gq/11 and PKC abolished PGE2-induced SOCE increase, indicating PGE2-induced SOCE enhancement is mediated by EP1 and its downstream Gq-PKC cascade. Our findings demonstrate that Orai1 plays an important role in mediating peripheral sensitization. Our study also provides new insight into molecular mechanisms underlying PGE2-induced modulation of inflammatory pain. R01NS087033, R01NS117484.