CRCNS Research Proposal: Collaborative Research: Mechanisms and dynamics of retronasal olfactory coding

CRCNS 研究提案：合作研究：鼻后嗅觉编码的机制和动力学

• 批准号: 1912352
• 负责人: Woodrow Shew
• 金额: $ 48.22万
• 依托单位: University of Arkansas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1912352&HistoricalAwards=false
• 关键词: CRCNS; Research; Proposal; Collaborative; Mechanisms

How do our brain, nose, and mouth work together to generate the flavor of food and drink? When flavor perception goes wrong, can this play a role in diseases like obesity? The sense of smell is very important for perceiving flavor, largely because of odors that originate in the mouth and are exhaled through the nose via the back of the throat in a a process called retronasal olfaction. In this study, researchers from the University of Arkansas, the Virginia Commonwealth University, and Southeastern Methodist University are teamed up to gain better understanding of how retronasal olfaction works using rats as an animal model. The researchers combine direct measurements of the brain in action together with computer simulations of air flow through the nose and neural networks. They are testing the idea that different forces in the nose caused by reversing airflow through the nasal cavity are responsible for how the brain distinguishes exhaled retronasal odors from inhaled odors. In addition, the researchers offer training opportunities at each of the three institutions and are developing an educational video game aimed at introducing users to basic concepts of neurobiology and cognitive neuroscience. Smells that enter the nose retronasally, i.e., from the back of the nasal cavity, play an essential role in flavor perception, yet many questions about the neuroscience of retronasal olfaction remain unanswered. How does simply reversing the direction of air flow through the nasal cavity result in different neural input to the olfactory bulb (OB)? How are retronasal and orthonasal (inhaled) olfactory signals encoded at the level of spiking neurons in the OB? How do interactions within OB circuits facilitate selective response to retronasal versus orthonasal stimuli? In this study, researchers from the University of Arkansas, the Virginia Commonwealth University, and Southeastern Methodist University are teamed up to answer these questions, guided by a two-part hypothesis. First, they hypothesize that, at the sensory periphery, retro- and orthonasal stimuli produce distinct spatiotemporal patterns of mechanosensory excitation of olfactory receptor neurons. Second, they hypothesize that, in the OB, cell-type-specific inhibitory circuit interactions are crucial for dynamic changes in retronasal coding. To test these hypotheses, the research team is combining high-density multi-electrode recordings in rat OB with fluid dynamics computer simulations based on the three-dimensional shape of the nasal cavity of the same animals. Moreover, the team is performing state-of-the-art realistic computational modeling to identify OB circuit-level principles of retronasal coding. This work is expected to generate new understanding of the neural basis of retronasal olfaction that includes both peripheral mechanisms in the nose and central mechanisms at the level of M/T cells in the OB. This project is jointly funded by the cross-directorate Collaborative Research in Computational Neuroscience program, the Established Program to Stimulate Competitive Research(EPSCoR), and the MPS Office of Multidisciplinary Activities.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.

我们的大脑，鼻子和嘴如何共同产生食物和饮料的味道？ 当风味感知出错时，这能在肥胖等疾病中发挥作用吗？ 气味对于感知风味非常重要，这主要是因为起源于口中的气味，并在称为后侧向嗅觉的过程中通过喉咙后部通过鼻子呼气。 在这项研究中，来自阿肯色大学，弗吉尼亚州英联邦大学和东南卫理公会大学的研究人员合作，以更好地了解如何使用大鼠作为动物模型的后肾后嗅觉。 研究人员将大脑在作用中的直接测量以及通过鼻子和神经网络流动的计算机模拟。他们正在测试这样的想法：通过鼻腔逆转气流引起的鼻子中的不同力是为了使大脑如何区分呼出的后肾后气味与吸入气味。此外，研究人员在三个机构中的每个机构中都提供培训机会，并正在开发一个旨在向用户介绍神经生物学和认知神经科学的基本概念的教育视频游戏。气味在鼻腔的背面向后进入鼻子，在风味感知中起着至关重要的作用，但是有关后肾后嗅觉神经科学的许多问题仍然没有得到解决。 简单地逆转通过鼻腔流动的方向导致嗅球（OB）的神经输入不同？ 在OB中尖峰神经元的水平上编码的鼻鼻和正直（吸入）嗅觉信号如何？ OB电路中的相互作用如何促进对腹侧与正直刺激的选择性反应？ 在这项研究中，来自阿肯色大学，弗吉尼亚州英联邦大学和东南卫理公会大学的研究人员合作回答了这些问题，并在两部分的假设的指导下。首先，他们假设，在感觉外围，恢复和正常刺激会产生嗅觉受体神经元的机械感觉激发的不同时空模式。 其次，他们假设在OB中，细胞型特异性抑制性电路相互作用对于腹侧编码的动态变化至关重要。 为了检验这些假设，研究团队正在将大鼠OB中的高密度多电极记录与基于同一动物鼻腔三维形状的流体动力学模拟相结合。此外，该团队正在执行最新的现实计算建模，以识别OB电路级编码的原理。 预计这项工作将产生对鼻后嗅觉的神经基础的新理解，其中包括OB中M/T细胞水平的鼻子和中心机制。该项目由计算神经科学计划的跨指导合作研究，启发竞争研究的既定计划（EPSCOR）和MPS多学科活动办公室共同资助。该奖项反映了NSF的法定任务，并通过该基金会的知识分子优点和广泛的影响来评估NSF的法定任务。

项目成果

Odor modality is transmitted to cortical brain regions from the olfactory bulb

• DOI: 10.1152/jn.00101.2023
• 发表时间: 2023-11-04
• 期刊: JOURNAL OF NEUROPHYSIOLOGY
• 影响因子: 2.5
• 作者: Craft，Michelle F.;Barreiro，Andrea K.;Ly，Cheng
• 通讯作者: Ly，Cheng

Collapse of complexity of brain and body activity due to excessive inhibition and MeCP2 disruption

• DOI: 10.1073/pnas.2106378118
• 发表时间: 2021-10-26
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Li，Jingwen;Kells，Patrick A.;Shew，Woodrow L.
• 通讯作者: Shew，Woodrow L.