Top-down (State dependent) Modulation of Sensory Processing in the Mouse Olfactory Bulb

大脑中的感觉处理并不是固定的，而是涉及信息流的逆流。在“自下而上”的通路中，感觉信息在从初级感觉传递到更高的大脑中心时被塑造和提炼。然而，信息也会被传递回来，影响更专门的大脑区域的感觉处理（“自上而下”处理）。通过自上而下的过程，经验、动机和期望等因素，即，一般的“大脑状态”，影响感觉处理，从而影响我们对世界的内部表征。然而，自上而下调节的神经元机制以及自上而下系统对复杂行为任务的相对贡献还没有得到很好的理解。为了研究感觉加工的自上而下调节，小鼠嗅觉通路是理想的脊椎动物模型系统：嗅觉通路是所有主要的顶级-羽绒系统和小鼠在很大程度上依赖嗅觉来定向，从而允许将定义的行为测试与各种各样的创新遗传工具相结合。这个为期一年的项目是基于埃米·诺特基金第一阶段获得的结果（见Zwischenevaluation），并将调查操纵清醒动物两个主要自上而下系统活动的行为后果。我们假设，在清醒的行为动物的自上而下的活动的外在调制将施加不同的影响知觉的歧视，因此，让我们测试自上而下的电路和行为表现之间的因果关系。总之，该项目旨在将我们在麻醉准备中获得的结果转移到清醒状态，因此代表了Emmy Noether项目的重要基石。

Sensory processing in the brain is not fixed and involves countercurrent streams of information flow. In the “bottom-up” pathway, sensory information is shaped and refined as it travels from primary sensory to higher brain centers. However, information is also relayed back to influence sensory processing in more specialized brain areas (“top-down” processing). Through top-down processes, factors like experience, motivation and expectation, i.e., the general “brain state”, affect sensory processing and, thereby, our internal representation of the world. However, the neuronal mechanism involved in top-down modulations and the relative contribution of top-down systems to complex behavioral tasks are not well understood.In order to study top-down modulations of sensory processing the mouse olfactory pathway is an ideal vertebrate model system: the olfactory pathway is targeted by all major top-down systems and mice largely rely on olfaction for orientation allowing defined behavioural tests to be combined with a wide variety of innovative genetic tools. This one year project is based on the results obtained during the first period of Emmy Noether funding (see Zwischenevaluation) and will investigate the behavioral consequences of manipulating activity of two major top-down systems for the awake animal. We hypothesize that an extrinsic modulation of top-down activity in the awake behaving animal will exert distinct effects on perceptual discrimination and therefore allow us to test for causal relationships between top-down circuits and behavioural performance. In summary, this project is aimed at transferring our results obtained in the anesthetised preparation to the awake condition and therefore represents an important cornerstone for the Emmy Noether project.