The Neural Basis of Audiovisual Temporal Processing and Perception: From Cortical Networks to Cellular Mechanisms

为了给我们提供更完整的感官体验，我们的大脑自然地融合了来自不同感官的信息。在听觉和视觉刺激相隔约100毫秒的情况下，我们通常会认为它们是同时发生的，即使它们实际上在时间上是相互抵消的。虽然这种时间紧密的视听刺激的整合可以提供某些行为优势，例如改进对环境中物体的检测、识别和定位，但时间整合的过于宽泛的窗口可能会产生问题，因为来自真正独立事件的信息可能不会被正确地感知。最近的人类研究表明，视听刺激的感知结合的准确性是由神经振荡调节的，特别是在视听皮层的γ波段（bb0 ~ 30hz）；这一现象被认为依赖于局部gaba能神经传递。然而，目前，特定的脑回路和细胞机制调节为视听知觉结合服务的假定振荡活动仍然难以捉摸，部分原因是该领域缺乏合适的动物模型进行侵入性研究。为了实现这一目标，我的实验室最近已经确定，大鼠是一个很好的模型，可以在单个神经元、局部微电路和感觉知觉的水平上研究视听时间处理的神经基础。例如，通过药理操作，我们发现大鼠视听皮质（V2L）中的gaba能神经传递不仅控制视听整合的精确时间，而且还影响感知结合发生的时间窗口。也就是说，考虑到局部gaba能微电路的复杂性和在皮质锥体神经元特定位置表达的各种GABA-A受体亚基，需要进一步的工作来揭示gaba能神经传递控制视听刺激时间整合为统一感知的细胞机制。在本研究中，我们将采用一种先进的方法，结合光遗传学/shRNA操作+行为大鼠体内电生理记录，以实现以下目标：(1)确定向V2L皮层的单感觉与多感觉丘脑皮质投射如何促进视听时间加工和感知；(2)研究V2L皮层gaba能中间神经元在视听时间加工和感知中的作用；(3)确定V2L皮层锥体神经元上表达的GABA-A受体亚基中，哪些特异的亚基参与了微调视听时间加工和感知。最终，考虑到我的实验室的专业知识、基础设施和最近的进展，世界上没有其他实验室有能力解决这个长期存在的问题：哺乳动物的大脑是如何将时间紧密的听觉和视觉刺激整合成一个统一的感知的？

In providing us with a more complete sensory experience, our brains naturally merge information from our different senses. In situations when an auditory and visual stimulus occur within ~100 ms of each other, we often perceive that they happened at the same moment, even though they were actually offset in time. Although this integration of closely-timed audiovisual stimuli can offer certain behavioural advantages, such as improved detection, identification and localization of objects in the environment, an overly broad window of temporal integration can be problematic, as information from truly separate events may not be correctly perceived as such. Recent human studies have suggested that the precision of perceptual binding of audiovisual stimuli is regulated by neural oscillations, especially in the gamma-band (>30 Hz), within the audiovisual cortex; a phenomenon that has been suggested to depend on local GABAergic neurotransmission. At present, however, the specific brain circuits and cellular mechanisms that regulate the putative oscillatory activity subserving audiovisual perceptual binding remain elusive, in part because the field has lacked suitable animal models for invasive studies. Toward that goal, my lab has recently established that rats represent an excellent model to study the neural basis of audiovisual temporal processing at the level of single neurons, local microcircuits and sensory perception. For example, using pharmacological manipulations, we revealed that GABAergic neurotransmission in the rat audiovisual cortex (V2L) not only controls the precise timing of audiovisual integration, but it also affects the window of time over which perceptual binding occurs. That said, given the complexity of the local GABAergic microcircuits and the various GABA-A receptor subunits expressed at specific locations on cortical pyramidal neurons, additional work is needed to uncover the cellular mechanisms by which GABAergic neurotransmission controls the temporal integration of audiovisual stimuli into a unified percept. In this proposal, we will use an advanced approach combining optogenetics/shRNA manipulation + in vivo electrophysiological recordings in behaving rats to address the following objectives: (1) To identify how unisensory vs. multisensory thalamocortical projections to the V2L cortex contribute to audiovisual temporal processing and perception; (2) To investigate the role of GABAergic interneurons within the V2L cortex on audiovisual temporal processing and perception, and; (3) To determine which of the specific GABA-A receptor subunits expressed on pyramidal neurons in V2L cortex are responsible for fine-tune audiovisual temporal processing and perception. Ultimately, given my lab's expertise, infrastructure and recent progress, no other lab in the world is as well-positioned to tackle the long-standing question: How does the mammalian brain integrate closely-timed auditory and visual stimuli into a unified percept?