Brainwide neural populations supporting multisensory decision-making

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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.