[PDF][PDF] Area postrema cell types that mediate nausea-associated behaviors

C Zhang, JA Kaye, Z Cai, Y Wang, SL Prescott… - Neuron, 2021 - cell.com
C Zhang, JA Kaye, Z Cai, Y Wang, SL Prescott, SD Liberles
Neuron, 2021cell.com
Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The
area postrema is implicated in some nausea responses and is anatomically privileged to
detect blood-borne 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 …
Summary
Nausea, the unpleasant sensation of visceral malaise, remains a mysterious process. The area postrema is implicated in some nausea responses and is anatomically privileged to detect blood-borne 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 to agonists of identified area postrema receptors were observed 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 toward understanding and therapeutically controlling nausea.
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