Top-down modulation of visual processing: mechanisms and functions

项目总结 即使在最早的大脑皮层阶段，视觉处理也受到内部产生的信息的影响。顶端- 在非常不同的行为背景下，可以发现向下对视觉处理的影响。因此，早期的视觉区域 越来越多地被认为是自下而上信息面对顶部的“界面”或“黑板” 拒绝交涉。然而，我们对自上而下信号的蜂窝和网络机制的了解 调节视皮层神经元的整合特性仍然是支离破碎的。此外，对视觉的影响 对早期视觉中描述的相对较小的自上而下调制的处理和视觉感知 大脑皮层是有争议的。最后，我们忽略了自顶向下调制在多大程度上是灵活的，并且可以适应于 新颖的行为目标。我们的长期目标是更好地理解自上而下的功能和机制 使用一个新的、易处理的模型对早期视觉加工的影响：视觉声音的调制 在V1中处理。我们最近已经证明，视觉的方向和方向的表示 在视听环境中，V1中的刺激通过增强神经元的反应而得到改善 与视觉线索的方向相匹配的优先方向，以及神经元活动的抑制 对正交方向和相反方向进行编码。此应用程序的总体目标是建立 声音调制对早期视觉调节的细胞和网络机制、功能影响和灵活性。 塞辛。基于我们的初步数据，我们的中心假设是V1中的声音调制是由 激活控制V1神经元定向和方向调节的局部机制，即适度的免疫抑制。 改善视觉刺激的表征可以改善视觉知觉，而声音调制在 V1是灵活的，可以通过训练适应新的行为目标。建议进行这项研究的理由 是为了更好地理解为什么、何时以及如何内部表征会偏向感官知觉。为了测试我们的中央 假设，我们提出了以下具体目标：1)确定细胞机制支持 全细胞记录对V1神经元的方位和方向依赖的声音调制 唤醒小鼠，这是我们实验室拥有独特专长的一种技术；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 视觉刺激在V1和视觉知觉上的表征；3)证明声音调制是 灵活，通过训练可以适应新的行为任务。我们的方法是创新的，因为我们 将为小鼠带来一个到目前为止主要在灵长类动物中解决的主题，以受益于功能成像、遗传 工具和我们在对清醒行为的小鼠进行全细胞记录方面的独特技能。拟议的研究 意义重大，因为它有望垂直推进我们对自上而下输入如何适应视觉的理解 对行为目标的处理。最终，这样的知识将为几种疾病的病理生理学提供信息。 发育性和退化性障碍，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.