Molecular mechanisms of the sense of touch

触觉的分子机制

• 批准号: 1923127
• 负责人: Sviatoslav Bagriantsev
• 金额: $ 100万
• 依托单位: Yale University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1923127&HistoricalAwards=false
• 关键词: Molecular; mechanisms; sense; touch

The ability to sense the world though physical contact is essential for all living organisms. The sense of touch is essential for navigation in the environment, object recognition, detection of pain and pleasure. It facilitates the establishment of maternal bonds and underlies the development of social behaviors. The sense of touch includes the sense of physical contact and temperature, but the mechanism is poorly understood. This project seeks to reveal molecular principles underlying the detection of physical touch, and understand how temperature influences this process. These studies will use tactile foraging ducks that allow examination of these general physiological problems through the perspective of a tactile specialist animal. This research will provide mechanistic insights into the process of touch detection and reveal general principles of mechanosensitivity in vertebrates. The broader impact activities aim to promote science among school students, with a focus on ethnic and socioeconomic groups underrepresented among scientists. The PI will reach out to schools in CT, MA and NY to teach how people feel touch, warmth and cold, how they see, smell or taste. Most of the trainees are female, underrepresented minorities, economically disadvantaged, or from families without prior college graduates. The activities are designed and implemented by undergraduates, PhD students and postdocs from the lab, under close supervision of the principal investigator. This approach provides a unique teaching experience to our lab members and help them advance professionally to become educator-researchers.In many vertebrates, fine tactile tasks are accomplished by organs covered with glabrous skin, such as the palm of hand in primates, or the bill of tactile foraging ducks. These organs specialize in the detection of the lightest forms of touch, such as transient contact and vibration, via mechanosensory corpuscles. How corpuscles convert touch into electrical signaling, what molecules are involved and how they work, remains largely unknown. The investigators will approach this problem by studying mechanosensitivity in the bill of tactile specialist ducks. They showed that duck bill contains numerous lamellar corpuscles innervated by trigeminal mechanoreceptors. Here, the investigator proposes to use the duck model to reveal general principles of touch detection by neuronal and non-neuronal components of mechanosensory corpuscles. This project aims to: (1) Determine the molecular basis of tactile-thermal interaction in neuronal mechanoreceptors. Mild cooling potentiates tactile acuity in vertebrates, but the mechanism is unknown. This project will test the hypothesis that cooling increases the ability of neuronal mechanoreceptors to convert touch into excitation, and identify the molecular basis of this process. (2) Investigate whether lamellar cells from Herbst (Pacinian) corpuscles can detect touch. It is well established that lamellar cells form a cushion around the neuronal core, acting as a passive mechanical filter. The investigator aims to test the hypothesis that lamellar cells are also mechanically sensitive, and are able to convert touch into excitation, actively contributing to the detection of touch.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

通过身体接触感知世界的能力对所有生物体都是必不可少的。触觉对于环境中的导航、物体识别、疼痛和愉悦的检测至关重要。它促进了母性纽带的建立，并成为社会行为发展的基础。触觉包括物理接触和温度的感觉，但其机制知之甚少。该项目旨在揭示物理触摸检测的分子原理，并了解温度如何影响这一过程。这些研究将使用触觉觅食鸭，允许通过触觉专家动物的角度来检查这些一般的生理问题。这项研究将提供机械的洞察力的过程中的触摸检测和揭示机械敏感性的脊椎动物的一般原则。更广泛的影响活动旨在促进在校学生的科学，重点是科学家中代表性不足的族裔和社会经济群体。PI将接触CT，MA和NY的学校，教人们如何感受触摸，温暖和寒冷，他们如何看到，闻到或尝到。大多数受训者是女性、代表性不足的少数民族、经济弱势群体或来自没有大学毕业生的家庭。这些活动由实验室的本科生、博士生和博士后在主要研究者的密切监督下设计和实施。这种方法为我们的实验室成员提供了独特的教学经验，并帮助他们专业地发展成为教育者和研究者。在许多脊椎动物中，精细的触觉任务是由覆盖着无毛皮肤的器官完成的，例如灵长类动物的手掌，或触觉觅食鸭的喙。这些器官专门通过机械感觉小体检测最轻微的触摸形式，例如短暂的接触和振动。小体如何将触摸转化为电信号，涉及哪些分子以及它们如何工作，在很大程度上仍然未知。研究人员将通过研究触觉专家鸭喙中的机械敏感性来解决这个问题。他们发现，鸭嘴兽包含许多由三叉神经机械感受器支配的板层小体。在这里，研究人员建议使用鸭子模型来揭示机械感觉小体的神经元和非神经元成分的触摸检测的一般原理。本研究的目的是：（1）确定神经元机械感受器中热-热相互作用的分子基础。温和的冷却增强脊椎动物的触觉敏锐度，但其机制尚不清楚。这个项目将测试的假设，冷却增加神经元机械感受器的能力，将触摸转化为兴奋，并确定这一过程的分子基础。(2)研究赫布斯特（Pacinian）小体的板层细胞是否可以检测触摸。已经确定的是，板层细胞在神经元核心周围形成缓冲垫，充当被动机械过滤器。该研究者的目的是验证板层细胞也具有机械敏感性的假设，并能够将触摸转化为兴奋，积极促进触摸的检测。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Mechanotransduction events at the physiological site of touch detection.

• DOI: 10.7554/elife.84179
• 发表时间: 2023-01-06
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Ziolkowski, Luke H.;Gracheva, Elena O.;Bagriantsev, Sviatoslav N.
• 通讯作者: Bagriantsev, Sviatoslav N.

Tactile sensation in birds: Physiological insights from avian mechanoreceptors.

• DOI: 10.1016/j.conb.2022.102548
• 发表时间: 2022-06
• 期刊: Current opinion in neurobiology
• 影响因子: 5.7

Osmolyte Depletion and Thirst Suppression Allow Hibernators to Survive for Months without Water

• DOI: 10.1016/j.cub.2019.07.038
• 发表时间: 2019-09-23
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Feng, Ni Y.;Junkins, Madeleine S.;Gracheva, Elena O.
• 通讯作者: Gracheva, Elena O.

Human TRPV1 structure and inhibition by the analgesic SB-366791.

• DOI: 10.1038/s41467-023-38162-9
• 发表时间: 2023-04-28
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Neuberger, Arthur;Oda, Mai;Nikolaev, Yury A.;Nadezhdin, Kirill D.;Gracheva, Elena O.;Bagriantsev, Sviatoslav N.;Sobolevsky, Alexander I.
• 通讯作者: Sobolevsky, Alexander I.

Lamellar cells in Pacinian and Meissner corpuscles are touch sensors.

Pacinian和Meissner体体中的层状细胞是触摸传感器。

• DOI: 10.1126/sciadv.abe6393
• 发表时间: 2020-12
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Nikolaev YA;Feketa VV;Anderson EO;Schneider ER;Gracheva EO;Bagriantsev SN
• 通讯作者: Bagriantsev SN