The parabrachial nucleus elicits a vigorous corticosterone feedback response to the pro-inflammatory cytokine IL-1ß.

The central nervous system regulates systemic immune responses by integrating the physiological and behavioral constraints faced by an individual. Corticosterone (CS), the release of which is controlled in the hypothalamus by the paraventricular nucleus (PVN), is a potent negative regulator of immune responses. Using the mouse model, we report that the parabrachial nucleus (PB), an important hub linking interoceptive afferent information to autonomic and behavioral responses, also integrates the pro-inflammatory cytokine IL-1ß signal to induce the CS response. A subpopulation of PB neurons, directly projecting to the PVN and receiving inputs from the vagal complex (VC), responds to IL-1ß to drive the CS response. Pharmacogenetic reactivation of these IL-1ß-activated PB neurons is sufficient to induce CS-mediated systemic immunosuppression. Our findings demonstrate an efficient brainstem-encoded modality for the central sensing of cytokines and the regulation of systemic immune responses.

Optimization of whole-brain rabies virus tracing technology for small cell populations.

The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0-3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.