Area postrema cell types that mediate nausea-associated behaviors

Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The area postrema is implicated in some nausea responses, and contains poorly understood brain-resident sensory neurons that are anatomically privileged to detect bloodborne signals. To investigate nausea mechanisms, we built an area postrema cell atlas through single-nucleus RNA sequencing, revealing a few neuron types. Using mouse genetic tools for cell-specific manipulation, we discovered excitatory neurons that induce nausea-related behaviors, with one neuron type mediating aversion imposed by multiple poisons. Nausea-associated responses were observed to agonists of identified area postrema receptors, and suppressed by targeted cell ablation and/or gene knockout. Anatomical mapping revealed a distributed network of long-range excitatory but not inhibitory projections with subtype-specific patterning. These studies reveal the basic organization of area postrema nausea circuitry, and provide a framework towards understanding and therapeutically controlling nausea. Single-nuclei sequencing of murine area postrema.