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

描述（由申请人提供）：食物的风味由来自多种感官形式的信息组成。一种主要的方式是嗅觉。在食物摄入过程中，是鼻后气味，而不是鼻前气味，告知食物的化学成分。 在人类的功能成像研究提供了重要的见解多模态风味整合的神经基础，并提供了支持的假设，大脑处理的ortho和retronasal气味不同。然而，人类的上游嗅球是不能用功能磁共振成像来检测的。有限的证据表明，在处理嗅觉信息的第一阶段，嗅球（OB），气味的神经表征在这两种嗅觉模式之间是不同的。然而，迄今为止，没有研究直接调查气味地图鼻后气味。事实上，所有关于脊椎动物延髓图的研究都只涉及鼻嗅。 除了鼻后地图仍然未知，它也仍然不清楚如何表示在肾小球中的第一个嗅觉突触转换。到目前为止，还没有研究明确地比较了突触前和突触后的反应。更一般地说，目前还不清楚光学成像的神经钙反应与突触后/突触后功能磁共振成像BOLD报告的那些相关。 为了填补这些空白，在我们的知识的味道编码和转换的OB和其翻译人类功能磁共振成像研究，我们建议在麻醉大鼠的鼻后和鼻前气味的图像地图。 我们提出了两组比较研究。在第一个目标中，我们将图像只有背OB在肾小球分辨率，只有正鼻反应，通过使用创新的微功能磁共振成像与相控线圈阵列，并通过使用突触前钙染料，以研究它们的神经生物学关系，在同一动物。在第二个目标中，我们将图像的反应，在整个OB的fMRI，和背侧OB光学钙成像，在同一动物的正鼻和鼻后气味。而fMRI可以访问整个OB，背侧OB的光学成像具有更高的空间和时间分辨率。对于这两种互补的方法，方法基本上是相同的，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，我们将对具有大范围亲脂性的一系列刺激的反应进行成像。我们将进一步研究气味流速和气味浓度对OB气味图的影响。 这些研究旨在提供关于鼻后嗅觉神经机制的新知识，以及使用大鼠模型的延髓神经转化，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.