PDF(Pubmed)
Abstract：
Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract (NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive (Calb1+) NTS neurons that are molecularly distinct from Tac1+ neurons. These Calb1+ neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+ NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.
摘要：
恶心和呕吐是应对侵入身体的病原体和毒素的重要防御反应。孤束核（NTS）对于启动这些反应很重要。然而,NTS的分子异质性和细胞多样性阻碍了对这些防御反应的更好理解。这里,我们构建了NTS细胞的单核转录组图谱,发现了可能参与这些防御性反应的多个NTS神经元群.其中,我们鉴定了Calbindin1阳性（Calb1+）NTS神经元，这些神经元在分子上不同于Tac1+神经元。这些Calb1神经元对于由蜡状芽孢杆菌分泌的呕吐毒素cereulide诱导的恶心和干涩至关重要。引人注目的是，我们发现cereulide可以直接调节支配Calb1+NTS神经元的迷走神经感觉神经元，一种不同于葡萄球菌肠毒素A引起的恶心和干馏的新机制，我们的NTS神经元转录组学图谱和功能分析揭示了cereulide诱导干馏样行为的神经机制。这些结果表明，大脑中的分子和细胞复杂性是对病原体和毒素多样性的防御反应的基础。
