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During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue 1 , 2 . Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPO LPS ) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPO LPS neurons. Finally, we show that VMPO LPS neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPO LPS neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection. A newly identified population of neurons in the ventral medial preoptic area of the hypothalamus regulate stereotypical symptoms of illness, including fever and appetite suppression.

Cross-discipline collaboration among state and local health departments improved foodborne illness surveillance for a 2018 Salmonella enterica serovar Enteritidis outbreak in Massachusetts, USA. Prompt linking of epidemiologic and laboratory data and implementation of in-state whole-genome sequencing and analysis improved public health surveillance capacity for outbreak detection and control.

Background Porcine reproductive and respiratory syndrome virus (PRRSV) causes a prolonged, economically devastating infection in pigs, and immune resistance to infection appears variable. Since the porcine adaptive immune system is not fully competent at birth, we hypothesized that age influences the dynamics of PRRSV infection. Thus, young piglets, growing 16-20-week-old finisher pigs, and mature third parity sows were infected with virulent or attenuated PRRSV, and the dynamics of viral infection, disease, and immune response were monitored over time. Results Virulent PRRSV infection and disease were markedly more severe and prolonged in young piglets than in finishers or sows. Attenuated PRRSV in piglets also produced a prolonged viremia that was delayed and reduced in magnitude, and in finishers and sows, about half the animals showed no viremia. Despite marked differences in infection, antibody responses were observed in all animals irrespective of age, with older pigs tending to seroconvert sooner and achieve higher antibody levels than 3-week-old animals. Interferon γ (IFN γ) secreting peripheral blood mononuclear cells were more abundant in sows but not specifically increased by PRRSV infection in any age group, and interleukin-10 (IL-10) levels in blood were not correlated with PRRSV infection status. Conclusion These findings show that animal age, perhaps due to increased innate immune resistance, strongly influences the outcome of acute PRRSV infection, whereas an antibody response is triggered at a low threshold of infection that is independent of age. Prolonged infection was not due to IL-10-mediated immunosuppression, and PRRSV did not elicit a specific IFN γ response, especially in non-adult animals. Equivalent antibody responses were elicited in response to virulent and attenuated viruses, indicating that the antigenic mass necessary for an immune response is produced at a low level of infection, and is not predicted by viremic status. Thus, viral replication was occurring in lung or lymphoid tissues even though viremia was not always observed.

Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods. The activity of these cells is necessary and sufficient for inducing food-seeking leading to subsequent consumption. Activation of vgat l/vlPAG cells produces exploratory foraging and compulsive eating without altering defensive behaviors. Moreover, l/vlPAG vgat cells are bidirectionally interconnected to several feeding, exploration and investigation nodes, including the zona incerta. Remarkably, the vgat l/vlPAG projection to the zona incerta bidirectionally controls approach towards food leading to consumption. These data indicate the PAG is not only a final downstream target of top-down exploration and foraging-related inputs, but that it also influences these behaviors through a bottom-up pathway. Periaqueductal gray (PAG) inputs control hunting, but foraging-inducing PAG cells were unidentified. Here, authors show that in mice activity in the projection of vgat PAG cells to the zona incerta is sufficient and necessary for food-seeking.

Spatial transcriptomics can link molecularly described cell types to their anatomical positions and functional roles. Moffitt et al. used a combination of single-cell RNA-sequencing and MERFISH (multiplexed error-robust fluorescence in situ hybridization) to map the identity and location of specific cell types within the mouse preoptic hypothalamus and surrounding areas of the brain (see the Perspective by Tasic and Nicovich). They related these cell types to specific behaviors via gene activity. The approach provides an unbiased description of cell types of the preoptic area, which are important for sleep, thermoregulation, thirst, and social behavior. Science , this issue p. eaau5324 ; see also p. 749 A spatially resolved single-cell transcriptomic study of an essential brain region yields a functionally annotated cell atlas. The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei—including the molecular identity, spatial organization, and function of distinct cell types—is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.

The midbrain periaqueductal gray (PAG) and hypothalamic preoptic area (POA) are essential for orchestrating instinctive behaviors. The current organization of the PAG into four main radial columns and the coarse nuclear organization of the POA lack the resolution needed to account for the vast range of functionalities displayed by these two large neural structures. Using single nuclear sequencing and spatially resolved single-cell transcriptomic measurements, we uncovered widespread transcriptional heterogeneity in the mouse PAG and POA with ~140 neuronal populations defined in the PAG and ~70 neuronal populations in the POA. Within the PAG, we used each population’s neighborhood properties to further assemble them into 19 discrete groups that share the same three-dimensional spatial motifs. We explored the transcriptional identity of PAG and POA cell types activated during various instinctive behaviors, and examined the spatial logic of PAG function, demonstrating the regional, yet selective recruitment of PAG cell types for distinct behaviors. Remarkably, certain behaviors trigger differential spatial activation patterns within a given cell type, illustrating the complexity of PAG molecular and functional 3D organization. Altogether, this work identifies novel neural spatial motifs and establishes new spatially informed functional and molecular maps of the POA and PAG during instinctive behavior.