Top-down modulation of visual processing: mechanisms and functions

项目摘要 即使在最早的皮层阶段，视觉处理也受到内部产生的信息的影响。顶部- 对视觉加工的影响在非常不同的行为环境中被发现。因此，早期的视觉区域 越来越多地被认为是“界面”或“黑板”，自下而上的信息在这里与自上而下的信息相遇， 向下表示。然而，我们对细胞和网络机制的知识， 调节视皮层神经元的整合特性仍然是零碎的。此外，对视觉的影响 在早期视觉系统中描述的相对较小的自上而下调制的处理和视觉感知 皮质是有争议的最后，我们忽略了自上而下的调制在多大程度上是灵活的，可以适应一个 新的行为目标。我们的长期目标是更好地理解自上而下的功能和机制 使用最近和易处理的模型对早期视觉处理的影响：视觉的声音调制 在V1中处理。我们最近已经表明，视觉的方向和方向的表示 V1中的刺激在视听环境中得到改善，通过增强神经元的反应， 与视觉线索的方向相匹配的优选方向，以及对神经元活动的抑制 正交方向和相反方向的编码。本申请的总体目标是建立 声音调制对早期视觉发育的细胞和网络机制、功能影响和灵活性， 切辛根据我们的初步数据，我们的中心假设是，V1的声音调制是由 激活控制V1神经元的方向和方向调谐的局部机制，即适度的免疫调节， 视觉刺激表征的改进可以改善视觉感知，并且声音调制在 V1非常灵活，可以通过培训来适应新的行为目标。拟议研究的理由 是为了更好地理解为什么，何时以及如何内部表征偏见感官知觉。为了测试我们的中央 假设，我们提出了以下具体目标：1）确定支撑 V1神经元的定向和方向依赖性声音调制，通过在 清醒小鼠，我们的实验室拥有独特的专业技术;使用双光子钙成像， 执行Go/NoGo行为任务的小鼠，我们还将2）确定声音调制对小鼠行为的影响。 视觉刺激在V1和视觉感知上的表现; 3）证明声音调制是 灵活的，可以通过训练来适应新的行为任务。我们的方法是创新的，因为我们 将给小鼠带来一个迄今为止主要在灵长类动物中讨论的主题，以从功能成像、遗传学和生物学中受益。 工具和我们在清醒行为小鼠中进行全细胞记录的独特技能。拟议研究 是重要的，因为它有望垂直推进我们对自上而下的输入如何适应视觉的理解 处理到行为目标。最终，这样的知识将告知几个去- 精神和退行性疾病，其中自上而下的感觉处理控制受损。

PROJECT SUMMARY Even at the earliest cortical stages, visual processing is influenced by internally generated information. Top- down influence on visual processing is found in very different behavioral contexts. As a result, early visual areas are increasingly considered as “interfaces” or “blackboards” where bottom-up information is confronted to top- down representations. Yet, our knowledge on the cellular and network mechanisms by which top-down signals modulate the integrative properties of visual cortical neurons is still fragmentary. Moreover, the impact on visual processing and visual perception of the relatively small top-down modulations that were described in early visual cortices is debated. Finally, we ignore to what extent top-down modulation is flexible and can be adapted to a novel behavioral goal. Our long-term goal is to better understand the functions and mechanisms of top-down influences on early visual processing using a recent and tractable model: the modulation by sound of visual processing in V1. We have recently shown that the representation of the orientation and direction of the visual stimulus in V1 is improved in the audiovisual context, through a potentiation of the response of neurons with preferred orientations matching the orientation of the visual cue, and a suppression of the activity of neurons coding for orthogonal orientations and opposite directions. The overall objective of this application is to establish the cellular and network mechanisms, functional impact and flexibility of sound modulation on early visual pro- cessing. Our central hypotheses, based on our preliminary data, is that sound modulation in V1 results from the activation of local mechanisms controlling the orientation and direction tuning of V1 neurons, that modest im- provements of the representation of visual stimuli can improve visual perception, and that sound modulation in V1 is flexible and can be adapted to novel behavioral goals by training. The rationale for the proposed research is to better understand why, when and how internal representations bias sensory perception. To test our central hypotheses, we propose the following specific aims: 1) Determine the cellular mechanisms underpinning the orientation and direction-dependent sound modulation of V1 neurons by performing whole-cell recordings in awake mice, a technique for which our laboratory has a unique expertise; Using two-photon calcium imaging in mice performing Go/NoGo behavioral tasks, we will also 2) Determine the impact of sound modulation on the representation of the visual stimulus in V1 and on visual perception; 3) Demonstrate that sound modulation is flexible and can be adapted to a novel behavioral task though training. Our approach is innovative because we will bring to the mouse a topic so far mostly addressed in primates to benefit from functional imaging, genetic tools and our unique skill at performing whole-cell recordings in awake behaving mice. The proposed research is significant because it is expected to vertically advance our understanding on how top-down inputs adapt visual processing to the behavioral goal. Ultimately, such a knowledge will inform the pathophysiology of several de- velopmental, and degenerative disorders in which top-down control of sensory processing is impaired.