Rostral ventromedial medulla (RVM)が嫌悪と不安を駆動するために外側視床下野（LHA）に投射する

Neurons in the LHA are critical drivers of behavioral and physiological responses to acute and chronic stress. However, the roles of the specific pre-synaptic inputs to the LHA in driving stress and resultant physiological effects are yet to be fully understood. Here, leveraging intersectional viral genetics, optogenetics, chemogenetics, and fiber photometry, we show that the excitatory projections from the RVM to LHA drive anxiety-like behaviors in male and female mice. This is a surprising finding since, traditionally, RVM has been studied in the context of opioidergic pain modulation through its inhibitory projections to the spinal cord. We find that the LHA neurons receiving inputs from the RVM, when activated, do not alter the nociceptive thresholds, yet are sufficient to drive anxiety-like behaviors. These LHA neurons are recruited by acute restraint, which is known to cause stress and anxiety. On the other hand, the LHA-projecting RVM neurons are responsive to both noxious thermal stimuli and acute restraint, promoting anxiety, yet with no effect on pain thresholds. Our findings provide evidence that a distinct ascending circuitry, from RVM to LHA, is instrumental in driving aversion and anxiety-like behaviors in mice without affecting nociceptive thresholds.Significance statement There is a strong link between pain and persistent anxiety, but the neural mechanisms underlying this relationship remain poorly understood. In this study, we reveal a novel neural pathway between the rostral ventromedial medulla (RVM) and lateral hypothalamic area (LHA) that can potentially convert painful experiences into anxiety. While the RVM is traditionally known for its role in opioidergic modulation of pain, our findings demonstrate that RVM neurons also contribute to the expression of anxiety-like behaviors.