부산대학교 도서관

Background Rodents utilize chemical cues to recognize and avoid other conspecifics infected with pathogens. Infection with pathogens and acute inflammation alter the repertoire and signature of olfactory stimuli emitted by a sick individual. These cues are recognized by healthy conspecifics via the vomeronasal or accessory olfactory system, triggering an innate form of avoidance behavior. However, the molecular identity of the sensory neurons and the higher neural circuits involved in the detection of sick conspecifics remain poorly understood. Results We employed mice that are in an acute state of inflammation induced by systemic administration of lipopolysaccharide (LPS). Through conditional knockout of the G-protein G[alpha]i2 and deletion of other key sensory transduction molecules (Trpc2 and a cluster of 16 vomeronasal type 1 receptors), in combination with behavioral testing, subcellular Ca.sup.2+ imaging, and pS6 and c-Fos neuronal activity mapping in freely behaving mice, we show that the G[alpha]i2.sup.+ vomeronasal subsystem is required for the detection and avoidance of LPS-treated mice. The active components underlying this avoidance are contained in urine whereas feces extract and two selected bile acids, although detected in a G[alpha]i2-dependent manner, failed to evoke avoidance behavior. Our analyses of dendritic Ca.sup.2+ responses in vomeronasal sensory neurons provide insight into the discrimination capabilities of these neurons for urine fractions from LPS-treated mice, and how this discrimination depends on G[alpha]i2. We observed G[alpha]i2-dependent stimulation of multiple brain areas including medial amygdala, ventromedial hypothalamus, and periaqueductal grey. We also identified the lateral habenula, a brain region implicated in negative reward prediction in aversive learning, as a previously unknown target involved in these tasks. Conclusions Our physiological and behavioral analyses indicate that the sensing and avoidance of LPS-treated sick conspecifics depend on the G[alpha]i2 vomeronasal subsystem. Our observations point to a central role of brain circuits downstream of the olfactory periphery and in the lateral habenula in the detection and avoidance of sick conspecifics, providing new insights into the neural substrates and circuit logic of the sensing of inflammation in mice. Keywords: LPS, Inflammation, Olfactory, Vomeronasal organ, G[alpha]i2, V1R, Ca.sup.2+ imaging, Dendritic knob, Avoidance behavior, Lateral habenula
Author(s): Jan Weiss[sup.1] , Hélène Vacher[sup.2] , Anne-Charlotte Trouillet[sup.2] , Trese Leinders-Zufall[sup.1] , Frank Zufall[sup.1] and Pablo Chamero[sup.2] Background Social behaviors facilitate interactions between conspecifics and increase the likelihood of […]