Loss of appetite or anorexia associated with inflammation impairs quality of life and increases morbidity in many diseases. However, the exact neural mechanism that mediates inflammation-associated anorexia is still poorly understood. Here we identified a population of neurons, marked by the expression of protein kinase C-delta, in the oval region of the bed nucleus of the stria terminalis (BNST), which are activated by various inflammatory signals. Silencing of these neurons attenuates the anorexia caused by these inflammatory signals. Our results demonstrate that these neurons mediate bidirectional control of general feeding behaviors. These neurons inhibit the lateral hypothalamus-projecting neurons in the ventrolateral part of BNST to regulate feeding, receive inputs from the canonical feeding regions of arcuate nucleus and parabrachial nucleus. Our data therefore define a BNST microcircuit that might coordinate canonical feeding centers to regulate food intake, which could offer therapeutic targets for feeding-related diseases such as anorexia and obesity.

Supplemental Digital Content is Available in the Text.Transmembrane protein 184B is necessary for the proper function of itch-sensitive sensory neurons involved in eczema through the control of Wnt pathway gene expression during development.

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Nociceptive and pruriceptive neurons in the dorsal root ganglia (DRG) convey sensations of pain and itch to the spinal cord, respectively. A sub-population of these neurons, marked by Somatostatin (Sst) expression, is responsible for sensing IL-31, a mediator of acute itch, atopic dermatitis, and asthma. Here we show that Tmem184b, a gene with known roles in axon degeneration and nerve terminal maintenance, is required for the expression of a large cohort of itch receptors such as those for IL-31, Leukotriene C4, and Histamine. Mice lacking Tmem184b fail to respond to IL-31, but maintain normal responses to pain and mechanical force, suggesting a specific defect in pruriception. Lineage-tracing studies using Sst-driven Cre recombinase show a loss of pruriceptive neurons in Tmem184b-mutant mice, indicating a defect in neuron subtype specification. Accordingly, Wnt-dependent transcriptional signatures and signaling components, which are essential for neuronal subtype specification during development, are markedly reduced in Tmem184b-mutant embryonic DRG. Lentiviral reexpression of Tmem184b in mutant embryonic neurons restores Wnt signatures, whereas reexpression of Tmem184b in adult DRG fails to restore itch responses. Together, these data demonstrate that Tmem184b promotes adult somatosensation through developmental Wnt signaling and specification of pruriceptive neurons.