Brainwide neural populations supporting multisensory decision-making

为了表现外部世界并做出适当的决定，大脑需要结合来自不同感觉模式的信息。无论是捕食者、猎物，还是试图安全过街的行人，这个过程都是无处不在的，也是至关重要的。但是，尽管多感官决策在自然环境中很普遍，但我们在很大程度上仍然不知道多模式信息流在大脑中的位置和方式。这部分是因为多感觉行为很难在实验室环境中健壮地再现，部分是因为多感觉决定涉及分散在大脑广泛区域的神经元，从技术上讲，记录所有这些区域是具有挑战性的。然而，随着啮齿动物行为和记录技术的新发展，我们现在能够以前所未有的效率处理多感觉决策背后的神经机制。我们的实验室最近为小鼠开发了一项多感觉行为任务，当它们转动轮子时，可以指示刺激是出现在左边还是右边。刺激可以是听觉的、视觉的或两者的组合。我们专门设计了这项行为任务，以与我们帮助开发的名为神经像素探针的新电生理学方法兼容。这些探头让我们可以记录大脑中任何地方数百个神经元的信息。通过将这两个发展结合起来，我们将回答关于多感官决策的长期问题。我们还可以创建第一个全脑地图来跟踪音频和视觉信号通过大脑传播并演变为老鼠的决定和行动。我们的第一个目标集中在早期感觉区域在多感觉决定中的作用。历史上，大脑皮层的某些区域被认为是单一感觉：它们代表着单一的感觉通道，比如视觉或听力。然而，最近的几项研究声称，这些区域对多种方式做出反应，视听整合的第一阶段发生在这些区域。我们将同时在行为正常的小鼠的两个区域--初级视觉皮质和听觉皮质--记录大量神经细胞。通过这些记录，我们可以最终测试这些区域是否包含多感觉信息，如果是，这些信息是否指导老鼠的行为。我们的第二个目标集中在多感觉区域中听觉和视觉信息是如何结合的。有人提出，多感觉大脑区域混合了视觉和听觉信息，使得一些神经元只对一种感觉模式做出反应，一些神经元对两种感觉模式都没有反应，而一小部分神经元对两种感觉模式都有反应。然而，这一假设是基于大脑的一个区域，我们现在怀疑这一区域并不是视听决定所必需的。因此，我们计划同时记录我们知道的行为所需的大脑区域，称为额叶皮质，以及更早的感觉区域。通过这个实验，我们将了解信息是如何在多感觉决策路径的早期和晚期区域之间转换的，并确定听觉和视觉信号是如何结合的。我们的最终目标是最雄心勃勃的：在老鼠执行行为任务时，创建一个视听信号的全脑地图。这张地图将包括来自大脑各个区域的约10万个神经元，这在几年前是无法实现的。这张地图将是无价的，原因有两个。它将确定大脑的哪些区域有可能代表老鼠的选择，因为这些区域必须包含多感觉神经元。此外，我们希望确定以前未被探索的多感觉整合区域，提供令人兴奋的新研究途径。这些实验结合了行为神经科学和电生理学的新发展，以获得对多感觉整合和决策背后的机制的前所未有的见解。

To represent the external world and make appropriate decisions, brains need to combine information from different sensory modalities. This process is ubiquitous and vital, whether predator, prey, or pedestrian trying to safely cross the street. But despite the prevalence of multisensory decisions in natural environments, we remain largely ignorant about where and how multimodal streams of information are combined in the brain. This is partly because multisensory behaviors are difficult to robustly recreate in a laboratory environment, and partly because multisensory decisions involve neurons dispersed across a wide set of brain regions, and it's technically challenging to record from all of them. However, with new developments in rodent behavior and recording technology, we are now able to tackle the neural mechanisms underlying multisensory decision-making with unprecedented efficacy.Our lab recently developed a multisensory behavioral task for mice where they turn a wheel to indicate whether a stimulus appeared on the left or right. The stimuli can be auditory, visual, or a combination of the two. We specifically designed this behavioral task to be compatible with new electrophysiology methods called Neuropixels probes, which we helped develop. These probes allow us to record from hundreds of neurons anywhere in the brain. By combining these two developments, we will answer longstanding questions about multisensory decision-making. We can also create the first brainwide map to trace the audio and visual signals as they propagate through the brain and evolve into the mouse's decision and action.Our first objective focuses on the role of early sensory regions in multisensory decisions. Historically, certain regions of cortex were considered unisensory: they represented a single sensory modality, like vision or audition. However, several recent studies have claimed that these regions respond to multiple modalities, and that the first stages of audiovisual integration happens in these areas. We will record large neural populations simultaneously in two of these areas-primary visual and auditory cortices-in behaving mice. With these recordings, we can conclusively test whether these regions contain multisensory information and if so, whether this information guides the behavior of the mouse.Our second objective focuses on how auditory and visual information is combined in multisensory regions. It's been proposed that multisensory brain regions mix visual and auditory information such that some neurons respond to only one sensory modality, some respond to neither, and a smaller fraction respond to both. However, this hypothesis was based on a region of the brain that we now suspect isn't required for audiovisual decisions. Thus, we plan to simultaneously record from a brain region we know to be required for the behavior, called frontal cortex, and earlier sensory regions. Through this experiment, we will understand how information is transformed between early and late regions in the multisensory decision-making pathway, and determine how auditory and visual signals are combined.Our final objective is our most ambitious: to create a brainwide map of audiovisual signals while mice perform the behavioral task. This map will comprise ~100,000 neurons from regions across the brain, something that would have been unachievable just a few years ago. This map will be invaluable for two reasons. It will establish which regions of the brain have the potential to represent the mouse's choice, because these regions must contain multisensory neurons. Further, we expect to identify previously unexplored regions of multisensory integration, providing exciting new avenues of research.Together, these experiments combine new developments in behavioral neuroscience and electrophysiology to gain unprecedented insights into the mechanisms underlying multisensory integration and decision-making.