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

我们的大脑、鼻子和嘴巴是如何协同工作来产生食物和饮料的味道的？当味觉出现问题时，这是否会导致肥胖等疾病？嗅觉对于感知味道非常重要，很大程度上是因为气味起源于口腔，然后通过喉咙后部通过鼻子呼出。这个过程叫做鼻后嗅觉。在这项研究中，来自阿肯色大学、弗吉尼亚联邦大学和东南卫理公会大学的研究人员联合起来，以老鼠为动物模型，更好地了解鼻后嗅觉是如何工作的。研究人员将大脑活动的直接测量与通过鼻子和神经网络的空气流动的计算机模拟结合起来。他们正在测试这样一种观点，即鼻腔内气流反向而产生的不同力量是大脑区分呼出的鼻后气味和吸入的气味的原因。此外，研究人员还在这三家机构提供培训机会，并正在开发一款教育视频游戏，旨在向用户介绍神经生物学和认知神经科学的基本概念。从鼻腔后部进入鼻子的气味在味道感知中起着至关重要的作用，然而关于后鼻嗅觉的神经科学的许多问题仍未得到解答。简单地改变气流通过鼻腔的方向是如何导致对嗅球（OB）的不同神经输入的？后鼻和正鼻（吸入）嗅觉信号是如何在OB的尖峰神经元水平上编码的？外耳部回路内的相互作用如何促进对鼻后刺激和鼻前刺激的选择性反应？在这项研究中，来自阿肯色大学、弗吉尼亚联邦大学和东南卫理公会大学的研究人员在一个两部分假设的指导下，联合起来回答这些问题。首先，他们假设，在感觉外围，逆鼻和正鼻刺激会产生不同的时空模式的嗅觉受体神经元的机械感觉兴奋。其次，他们假设，在OB中，细胞类型特异性抑制回路的相互作用对后鼻编码的动态变化至关重要。为了验证这些假设，研究小组将大鼠OB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计算机模拟相结合。此外，该团队正在进行最先进的现实计算建模，以确定OB电路级的后鼻编码原理。这项工作有望对鼻后嗅觉的神经基础产生新的认识，包括鼻子的外周机制和OB中M/T细胞水平的中枢机制。该项目由计算神经科学跨部门合作研究计划、刺激竞争研究的既定计划（EPSCoR）和MPS多学科活动办公室共同资助。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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 ? 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.