Multimodal flavor integration and retronasal olfaction in the mouse

 描述(由申请人提供)：味觉和气味刺激如何整合以及鼻后气味如何处理是味道神经科学的两个基本问题。人类的功能成像研究为多模式风味整合的神经基础提供了重要的见解，但无法解决需要更高时空分辨率或神经活动或经验的实验操作的问题，也无法评估人类嗅球(OB)。为了解决这些局限性，本项目的目标是建立转基因小鼠作为一种新的气味模型，并研究气味整合和鼻后气味的神经机制。我们现在已经证实，小鼠和大鼠的鼻后嗅觉与人类的一样。第一项研究将使用光学钙成像来测量嗅球中与口服气味相关的时空模式，方法是通过清醒的头部固定的转基因GCaMP小鼠执行气味检测任务。我们还将探索携带移动头盔微型成像显微镜的自由活动小鼠的神经行为谱系。气味特性、主动采样(嗅探)、摄取(吞咽)、饥饿和依赖味道体验的气味-味觉整合对鼻后OB反应的影响将在食物探索、接近和摄取过程中进行评估。我们现在已经确定OB的时间动力学，即肾小球之间的相对起始延迟，可以被小鼠检测到低至15ms。为了确定OB中的鼻后时间信息是否有助于下游过程，我们将询问光基因修饰小鼠在嗅觉周期的不同阶段的时间辨别阈值是什么。接下来，我们将询问回放到OB上的逆鼻OB活动的动态是否可区分。最后，我们将询问不同的肾小球发病序列是否可区分。重要的是，我们将评估这三个措施如何依赖于嗅探阶段。总而言之，这些研究旨在利用实验上强大的转基因小鼠模型，从根本上提供关于味道感知的神经机制的新知识。

 DESCRIPTION (provided by applicant): How taste and odor stimuli become integrated and how retronasal odorants are processed are two fundamental questions in flavor neuroscience. Functional imaging studies in humans have provided important insights into the neural bases of multimodal flavor integration, yet cannot address issues requiring higher spatio-temporal resolution or experimental manipulation of neural activity or of experience, nor evaluate the human olfactory bulb (OB). To address these limitations, the goal of the present project is to establish the transgenic mouse as a novel flavor model and to investigate the neural mechanisms of flavor integration and retronasal smell. We have now established that retronasal olfaction occurs in mice and rats as it does in humans. A first study will employ optical calcium imaging to measure spatio-temporal patterns evoked in the olfactory bulb associated with the oral ingestion of odorants by awake head-fixed transgenic GCaMP mice performing an odor detection task. We will also explore the neuro-behavioral repertoire of free-moving mice carrying a mobile head-mounted miniature imaging microscope. The effects of odor properties, active sampling (sniffing), ingestion (swallowing), hunger and flavor-experience dependent odor-taste integration on retronasal OB responses will be assessed during food exploration, approach and ingestion. We have now established that the temporal dynamics of the OB, i.e. the relative onset delays among glomeruli, are detectable by mice down to 15 ms. To determine whether retronasal temporal information in the OB, which differs fundamentally between ortho- and retronasal smell, contributes to downstream processes, we will ask what the temporal discrimination thresholds are for optogenetically modified mice during various phases of the sniff-cycle. We will next ask whether the dynamics of retronasal OB activity played back onto the OB is discriminable. Last, we will ask if different glomerular onset sequences are discriminable. Importantly, we will assess how these three measures depend on sniff-phase. Together these studies are intended to provide fundamentally new knowledge about the neural mechanisms of flavor perception using the experimentally powerful transgenic mouse models.