Unconventional receptor neurons in nasal epithelia

描述(申请人提供)：脊椎动物的鼻部上皮在检测我们环境中的化学线索方面发挥着重要作用，如与食物有关的气味、性和非性社交、捕食者和危险。通常的观点将纤毛感受器神经元归因于主要的嗅觉上皮，以检测食物气味，并将微绒毛感受器神经元归因于犁鼻器，以探测性/社会暗示。呼吸道上皮被认为只含有三叉神经的游离神经末梢来检测潜在的有害物质；然而，最近的研究以及我们的初步数据表明，鼻上皮的形态和功能更加复杂。我们的初步数据表明，啮齿类动物和人类的主要嗅觉上皮含有与纤毛感受器神经元描述不符的受体细胞，而呼吸上皮含有几种类型的感觉细胞。由于这些细胞大量存在(例如，主嗅觉上皮中的微绒毛细胞占5%)，它们代表了一个生理上相关的群体，其功能可能在化学感觉中发挥重要作用。根据我的初步数据，我推测人类和啮齿动物的主要嗅觉上皮细胞含有非常规细胞，如隐窝嗅觉感受器神经元，到目前为止只在鱼类中描述过，呼吸上皮细胞含有几种类型的孤立化学感觉细胞。这项应用的目标是确定这些非常规受体细胞的特征。我的实验旨在清楚地了解它们的解剖和生化特征，以便将来进行功能实验。我们将利用人和啮齿动物鼻部组织成熟的免疫细胞化学和超微结构(扫描和透射电子显微镜)技术来确定这些细胞的神经元特性和形态特征。综上所述，这些实验将使人们对鼻腔上皮细胞中存在的感觉细胞类型有更详细的了解，从而有助于进一步研究它们的功能。为了了解嗅觉系统的紊乱和疾病，如头部创伤或癌症治疗、阿尔茨海默氏症或帕金森氏症引起的嗅觉障碍，以及设想可能的治疗方法，彻底了解参与气味检测的细胞类型是至关重要的。

DESCRIPTION (provided by applicant): The nasal epithelia of vertebrates play important roles in the detection of chemical cues in our environment such as odorants related to food, sexual and non-sexual social interaction, predators, and hazards. The common view attributes ciliated receptor neurons to the main olfactory epithelium to detect mainly food odors and microvillus receptor neurons to the vomeronasal organ to detect sexual/social cues. The respiratory epithelium is said to contain only free nerve endings of the trigeminal nerve to detect potentially noxious substances; however, recent studies, as well as our preliminary data, show that morphology and function of the nasal epithelia are more complex. Our preliminary data indicate that the main olfactory epithelium of rodents and humans contains receptor cells that do not match the description of ciliated receptor neurons and that the respiratory epithelium contains several types of sensory cells. As these cells occur in considerable numbers (e.g., microvillus cells in the main olfactory epithelium > 5%), they represent a physiologically relevant population whose function may play an important role in chemosensation. Based on my preliminary data, I hypothesize that the main olfactory epithelia of humans and rodents contain unconventional cells, such as the crypt olfactory receptor neuron, hitherto only described for fish and that the respiratory epithelia contain several types of solitary chemosensory cells. The goal of this application is to characterize these unconventional receptor cells. My experiments are designed to obtain a clear picture of their anatomical and biochemical features to enable future functional experiments. Well-established immunocytochemical and ultrastructural (scanning and transmission electron microscopy) techniques on human and rodent nasal tissue will be utilized to determine the neuronal properties and morphological characteristics of these cells. Taken together, these experiments will render a more detailed knowledge of the sensory cell types present in the nasal epithelia, and thus, facilitate further studies on their function. A thorough knowledge of the cell types involved in the detection of odorants is critical in order to understand disorders and diseases of the olfactory system, such as anosmia caused by head trauma or cancer treatment, Alzheimer's or Parkinsonian diseases, and to conceive possible remedies.