Abstract:
Electrical excitability-the ability to fire and propagate action potentials-is a signature feature of neurons. How neurons become excitable during development and whether excitability is an intrinsic property of neurons remain unclear. Here, we demonstrate that Schwann cells, the most abundant glia in the peripheral nervous system, promote somatosensory neuron excitability during development. We find that Schwann cells secrete prostaglandin E2, which is necessary and sufficient to induce developing somatosensory neurons to express normal levels of genes required for neuronal function, including voltage-gated sodium channels, and to fire action potential trains. Inactivating this signaling pathway in Schwann cells impairs somatosensory neuron maturation, causing multimodal sensory defects that persist into adulthood. Collectively, our studies uncover a neurodevelopmental role for prostaglandin E2 distinct from its established role in inflammation, revealing a cell non-autonomous mechanism by which glia regulate neuronal excitability to enable the development of normal sensory functions.
摘要:
电兴奋性-激发和传播动作电位的能力-是神经元的特征。神经元在发育过程中如何变得兴奋以及兴奋性是否是神经元的内在属性尚不清楚。这里,我们证明了施万细胞,周围神经系统中最丰富的胶质细胞,在发育过程中促进体感神经元的兴奋性。我们发现雪旺氏细胞分泌前列腺素E2,这对于诱导发育中的体感神经元表达神经元功能所需的正常水平的基因是必要和充分的,包括电压门控钠通道,并发射动作电位列车。在雪旺细胞中激活该信号通路会损害体感神经元的成熟,导致持续到成年的多模态感觉缺陷。总的来说,我们的研究揭示了前列腺素E2的神经发育作用与其在炎症中的既定作用不同,揭示了神经胶质调节神经元兴奋性以实现正常感觉功能发育的细胞非自主机制。