Immune stimulation induces Fos expression in brainstem amygdala afferents

Adaptation to infectious diseases or models of infectious diseases such as immune stimulation with exogenous administration of bacterial lipopolysaccharide (LPS) or cytokines involve complex autonomic, endocrine, and behavioral responses mediated by the central nervous system. The purpose of this study is to determine the neural pathways from the brainstem activating the central nucleus of the amygdala after LPS injections in rats. Fos immunohistochemistry was performed as a marker of neuronal activation in rats prepared with injections of the retrograde tracing agents Fluorogold or cholera toxin B subunit directed at the central nucleus of the amygdala, and subsequently treated with intravenous LPS. The dose of LPS was titrated to achieve behavioral suppression ("sickness behavior") and fever, while avoiding hypotension and shock. Low-dose LPS induced Fos in central amygdala afferent neurons in the periaqueductal gray, lateral parabrachial nucleus, and solitary nucleus, as indicated by neurons containing both Fos and retrograde tracing agent. The lateral parabrachial nucleus had approximately 10-fold higher numbers of double-labeled cells than the solitary nucleus and periaqueductal gray; 95% of the double-labeled neurons in the lateral parabrachial nucleus were located in the outer zone of the external lateral subnucleus. These results suggest that a prominent source of limbic activation from the brainstem after LPS involves a restricted subdivision of the lateral parabrachial nucleus.