Brainwide neural populations supporting multisensory decision-making

为了表征外部世界并做出适当的决定，大脑需要将来自不同感觉模态的信息联合收割机组合起来。这个过程是无处不在的和至关重要的，无论是捕食者，猎物，或行人试图安全地过马路。但是，尽管多感官决策在自然环境中很普遍，我们仍然在很大程度上不知道多模态信息流在大脑中的何处以及如何组合。这部分是因为多感官行为很难在实验室环境中稳健地重现，部分是因为多感官决策涉及分散在广泛的大脑区域的神经元，并且从所有这些区域记录下来在技术上具有挑战性。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解决多感官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官行为任务，让它们转动轮子来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。我们专门设计了这个行为任务，以兼容我们帮助开发的称为神经像素探针的新电生理学方法。这些探针使我们能够记录大脑中任何地方的数百个神经元。通过结合这两个发展，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追踪听觉和视觉信号在大脑中传播并演变成老鼠的决定和行动。我们的第一个目标是关注早期感觉区域在多感觉决定中的作用。从历史上看，大脑皮层的某些区域被认为是单一的：它们代表一种单一的感觉方式，如视觉或听觉。然而，最近的几项研究声称，这些地区对多种模式作出反应，视听融合的第一阶段发生在这些地区。我们将同时记录表现良好的老鼠的两个区域初级视觉和听觉皮层的大量神经元。有了这些记录，我们可以最终测试这些区域是否包含多感官信息，如果是这样，这些信息是否指导小鼠的行为。我们的第二个目标集中在听觉和视觉信息是如何在多感官区域结合。有人提出，多感觉大脑区域混合了视觉和听觉信息，因此一些神经元只对一种感觉方式做出反应，一些神经元对两种感觉方式都没有反应，而一小部分神经元对两种感觉方式都有反应。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不需要视听决策。因此，我们计划同时记录我们知道的行为所需的大脑区域，称为额叶皮层，以及早期的感觉区域。通过这个实验，我们将了解信息是如何在多感觉决策通路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。我们的最终目标是我们最雄心勃勃的：在小鼠执行行为任务时创建一个全脑视听信号地图。这张地图将包含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，原因有二。它将确定大脑的哪些区域具有代表小鼠选择的潜力，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开发的区域的多感觉整合，提供令人兴奋的新途径的research.Together，这些实验联合收割机结合行为神经科学和电生理学的新发展，以获得前所未有的深入了解多感觉整合和决策的机制。

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.