Hirata Harumitsu, Mizerska Kamila, Dallacasagrande Valentina, Guaiquil Victor H, Rosenblatt Mark I
Department of Ophthalmology, Weill Cornell Medical College, New York, New York; and
Department of Ophthalmology, Weill Cornell Medical College, New York, New York; and.
J Neurophysiol. 2017 May 1;117(5):1935-1947. doi: 10.1152/jn.00925.2016. Epub 2017 Mar 1.
It is widely accepted that the mechanisms for transducing sensory information reside in the nerve terminals. Occasionally, however, studies have appeared demonstrating that similar mechanisms may exist in the axon to which these terminals are connected. We examined this issue in the cornea, where nerve terminals in the epithelial cell layers are easily accessible for debridement, leaving the underlying stromal (axonal) nerves undisturbed. In isoflurane-anesthetized rats, we recorded extracellularly from single trigeminal ganglion neurons innervating the cornea that are excited by ocular dryness and cooling: low-threshold (<2°C cooling) and high-threshold (>2°C) cold-sensitive plus dry-sensitive neurons playing possible roles in tearing and ocular pain. We found that the responses in both types of neurons to dryness, wetness, and menthol stimuli were effectively abolished by the debridement, indicating that their transduction mechanisms lie in the nerve terminals. However, some responses to the cold, heat, and hyperosmolar stimuli in low-threshold cold-sensitive plus dry-sensitive neurons still remained. Surprisingly, the responses to heat in approximately half of the neurons were augmented after the debridement. We were also able to evoke these residual responses and follow the trajectory of the stromal nerves, which we subsequently confirmed histologically. The residual responses always disappeared when the stromal nerves were cut at the limbus, suggesting that the additional transduction mechanisms for these sensory modalities originated most likely in stromal nerves. The functional significance of these residual and enhanced responses from stromal nerves may be related to the abnormal sensations observed in ocular disease. In addition to the traditional view that the sensory transduction mechanisms exist in the nerve terminals, we report here that the proximal axons (stromal nerves in the cornea from which these nerve terminals originate) may also be capable of transducing sensory information. We arrived at this conclusion by removing the epithelial cell layers of the cornea in which the nerve terminals reside but leaving the underlying stromal nerves undisturbed.
人们普遍认为，感觉信息的转导机制存在于神经末梢。然而，偶尔也会有研究表明，在与这些末梢相连的轴突中可能存在类似的机制。我们在角膜中研究了这个问题，角膜上皮细胞层中的神经末梢很容易进行清创处理，而其下方的基质（轴突）神经不受影响。在异氟烷麻醉的大鼠中，我们从支配角膜的单个三叉神经节神经元进行细胞外记录，这些神经元会因眼干和冷却而兴奋：低阈值（<2°C冷却）和高阈值（>2°C）的冷敏加干敏神经元可能在流泪和眼痛中起作用。我们发现，清创处理有效地消除了这两种类型神经元对干燥、湿润和薄荷醇刺激的反应，表明它们的转导机制存在于神经末梢。然而，低阈值冷敏加干敏神经元对冷、热和高渗刺激的一些反应仍然存在。令人惊讶的是，清创处理后，约一半神经元对热的反应增强了。我们还能够诱发这些残留反应并追踪基质神经的轨迹，随后通过组织学进行了确认。当在角膜缘切断基质神经时，残留反应总是消失，这表明这些感觉模态的额外转导机制很可能起源于基质神经。这些来自基质神经的残留和增强反应的功能意义可能与眼部疾病中观察到的异常感觉有关。除了感觉转导机制存在于神经末梢的传统观点外，我们在此报告，近端轴突（角膜中这些神经末梢起源的基质神经）也可能能够转导感觉信息。我们通过去除神经末梢所在的角膜上皮细胞层但不干扰其下方的基质神经得出了这一结论。
