Infections induce a set of pleiotropic responses in animals, including anorexia, adipsia, lethargy and changes in temperature, collectively termed sickness behaviours¹. Although these responses have been shown to be adaptive, the underlying neural mechanisms have not been elucidated^2,3,4. Here we use of a set of unbiased methodologies to show that a specific subpopulation of neurons in the brainstem can control the diverse responses to a bacterial endotoxin (lipopolysaccharide (LPS)) that potently induces sickness behaviour. Whole-brain activity mapping revealed that subsets of neurons in the nucleus of the solitary tract (NTS) and the area postrema (AP) acutely express FOS after LPS treatment, and we found that subsequent reactivation of these specific neurons in FOS^2A-iCreERT2 (also known as TRAP2) mice replicates the behavioural and thermal component of sickness. In addition, inhibition of LPS-activated neurons diminished all of the behavioural responses to LPS. Single-nucleus RNA sequencing of the NTS–AP was used to identify LPS-activated neural populations, and we found that activation of ADCYAP1⁺ neurons in the NTS–AP fully recapitulates the responses elicited by LPS. Furthermore, inhibition of these neurons significantly diminished the anorexia, adipsia and locomotor cessation seen after LPS injection. Together these studies map the pleiotropic effects of LPS to a neural population that is both necessary and sufficient for canonical elements of the sickness response, thus establishing a critical link between the brain and the response to infection.

感染会引起动物的一系列多效反应，包括厌食、嗜睡、嗜睡和温度变化，统称为疾病行为¹。虽然这些反应已被证明是适应性的，但潜在的神经机制尚未阐明^2,3,4。在这里，我们使用一组公正的方法来证明脑干中特定的神经元亚群可以控制对有效诱导疾病行为的细菌内毒素（脂多糖 (LPS)）的多种反应。全脑活动图显示孤束核 (NTS) 和后区 (AP) 中的神经元亚群在 LPS 治疗后急性表达 FOS，我们发现这些特定神经元在 FOS 中的后续再激活^2A-iCreERT2（也称为 TRAP2）小鼠复制疾病的行为和热成分。此外，抑制 LPS 激活的神经元减少了对 LPS 的所有行为反应。NTS-AP 的单核 RNA 测序用于识别 LPS 激活的神经群，我们发现 NTS-AP 中 ADCYAP1 ⁺神经元的激活完全概括了 LPS 引发的反应。此外，对这些神经元的抑制显着减少了 LPS 注射后出现的厌食、肥胖和运动停止。这些研究共同将 LPS 的多效性影响映射到神经群体，这对于疾病反应的规范元素是必要和充分的，从而在大脑和对感染的反应之间建立了关键联系。