Bulbar maps to retronasal smell by optical calcium imaging and fMRI in acute rat

描述（由申请人提供）：食物的味道是由多种感官模式的信息组成的。一种主要的形态是嗅觉。在食物摄入过程中，是后鼻气味，而不是正鼻气味告诉我们食物的化学成分。人类的功能成像研究为多模态风味整合的神经基础提供了重要的见解，并为大脑对正鼻和后鼻气味的处理不同的假设提供了支持。然而，人类的上游嗅球是无法通过fMRI检测到的。有限的证据表明，在处理嗅觉信息的第一阶段，即嗅球（OB），气味的神经表征在这两种气味模式之间是不同的。然而，到目前为止，还没有研究直接调查气味映射到鼻后嗅觉。实际上，每一项关于脊椎动物球茎图的研究都只针对正鼻嗅觉。除了后鼻图仍然未知之外，表征是如何在肾小球的第一嗅觉突触中转化的也仍然不清楚。迄今为止，还没有研究明确地比较了OB的突触前和突触后反应。更一般地说，光学成像的神经钙反应与突触周围/突触后fMRI BOLD报告的神经钙反应之间的关系尚不清楚。为了填补我们对OB中气味编码和转换及其对人类功能磁共振成像研究的认识空白，我们建议对麻醉大鼠的后鼻和正鼻气味图进行成像。我们提出两组比较研究。在第一个目标中，我们将在肾小球分辨率下仅对OB背侧进行成像，通过使用具有相控线圈阵列的创新微功能磁共振成像和使用突触前钙染料，在同一动物中研究它们的神经生物学关系。在第二个目标中，我们将在同一动物中使用功能磁共振成像成像对整个OB的正鼻和后鼻气味的反应，以及OB背光学钙成像。而功能磁共振成像可以访问整个OB， OB背的光学成像具有更高的空间和时间分辨率。对于两种互补的方法，方法本质上是相同的，唯一允许我们比较两种技术得出的气味图。为了进一步了解与嗅觉相关的参数的影响，我们将对一系列具有大亲脂性的刺激的反应进行成像。我们将进一步研究气味流率和气味浓度对OB气味图谱的影响。这些研究旨在提供关于后鼻气味的神经机制的新知识，以及使用大鼠模型的球神经转换，这些研究是将啮齿动物功能成像转化为人类嗅觉fMRI研究的第一步。

DESCRIPTION (provided by applicant): The flavor of a food is comprised of information from multiple sensory modalities. One major modality is the sense of smell. During food ingestion it is the retronasal smell, not the orthonasal route that informs about the chemical make-up of food. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, and provided support for the hypothesis that brain processing of ortho- and retronasal smell differs. Yet, the upstream olfactory bulbs of humans are not accessible to fMRI. Limited evidence suggests that the neural representations of odorants at the first stage of processing olfactory information, the olfactory bulb (OB), differ between these two modes of smell. However, to date no study has directly investigated odor maps to retronasal smell. Virtually every study on bulbar maps in vertebrates is on orthonasal smell only. In addition to the retronasal maps remaining unknown, it also remains unclear how representations are transformed across the first olfactory synapse in the glomerulus. To date no study has unambiguously compared presynaptic and postsynaptic responses in OB. More generally, it remains unclear how optically imaged neural calcium responses relate to those reported by peri/post-synaptic fMRI BOLD. To fill in these gaps in our knowledge of flavor encoding and transformation in the OB and its translation to human fMRI studies, we propose to image retronasal and orthonasal odor maps in the anesthetized rat. We propose two comparative sets of studies. In the first Aim, we will image only the dorsal OB at glomerular resolution to only orthonasal responses by using innovative micro-fMRI with phased coil arrays and by using presynaptic calcium dyes, to investigate their neurobiological relation, in the same animal. In the second Aim we will image responses to both orthonasal and retronasal odors across the entire OB with fMRI, and the dorsal OB optical calcium imaging, in the same animal. Whereas fMRI has access to the entire OB, optical imaging of the dorsal OB has a higher spatial and temporal resolution. For both complementary approaches the methods will be essentially the same, uniquely allowing us to compare the odor maps derived by both techniques. To further understand the effects of parameters relevant to olfaction, we will image responses to an array of stimuli with a large span of lipophilicity. We will furthermore investigate the effects of odor flow rate and odor concentration on the odor maps of the OB. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of retronasal smell, and of bulbar neural transformations using a rat model and these studies are a first step toward translation of rodent functional imaging to human olfactory fMRI research. PUBLIC HEALTH RELEVANCE: This project investigates the neural encoding of retronasal smell. Retronasal smell forms an obligatory and important aspect of the flavor of food. Because flavor plays a central role in motivating food intake, research on the neural mechanisms of flavor perception is essential for understanding the sensory factors that contribute to eating-related disorders such as obesity, diabetes and cardiovascular disease.