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加工是味觉神经科学中的两个基本问题。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，但不能解决需要更高的时空分辨率或神经活动或经验的实验操作的问题，也不能评估人类嗅球（OB）。为了解决这些问题，本项目的目标是建立一个新的风味模型的转基因小鼠，并探讨风味整合和鼻后嗅觉的神经机制。我们现在已经确定，鼻后嗅觉发生在小鼠和大鼠，因为它在人类。第一项研究将采用光学钙成像来测量与清醒的头部固定的转基因GCaMP小鼠执行气味检测任务的气味的口服摄入相关的嗅球中诱发的时空模式。我们还将探索携带移动的头戴式微型成像显微镜的自由移动小鼠的神经行为库。气味特性，主动采样（嗅），摄入（吞咽），饥饿和风味经验依赖的气味-味觉整合对鼻后OB反应的影响将在食物探索，方法和摄入过程中进行评估。我们现在已经确定，OB的时间动态，即肾小球之间的相对起始延迟，可由小鼠检测到低至15 ms。为了确定OB中的鼻后时间信息（其在鼻后嗅觉和鼻后嗅觉之间根本不同）是否有助于下游过程，我们将询问在嗅闻周期的各个阶段期间，光遗传学修饰的小鼠的时间辨别阈值是多少。我们接下来要问的是，鼻后OB的动态活动是否可以通过OB进行区分。最后，我们将询问不同的肾小球发病序列是否是可辨别的。重要的是，我们将评估这三个指标如何依赖于嗅探阶段。总之，这些研究的目的是提供从根本上新的知识的神经机制的味道感知使用实验强大的转基因小鼠模型。

 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.