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

视听时间处理和感知的神经基础：从皮质网络到细胞机制

• 批准号: RGPIN-2019-06085
• 负责人: Allman, Brian
• 金额: $ 4.01万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=690638
• 关键词: Neural; Basis; Audiovisual; Temporal; Processing

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?

在为我们提供更完整的感官体验时，我们的大脑自然地融合了来自不同感官的信息。当听觉和视觉刺激发生在100毫秒内时，我们通常会认为它们发生在同一时刻，即使它们实际上在时间上是偏移的。尽管这种紧密定时的视听刺激的整合可以提供某些行为优势，例如改进环境中物体的检测、识别和定位，但过宽的时间整合窗口可能会出现问题，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精确性受到视听皮层内的神经振荡的调节，特别是在γ波段（>30 Hz）;这种现象被认为取决于局部GABA能神经传递。然而，目前，特定的脑回路和细胞机制，调节假定的振荡活动subserving视听知觉绑定仍然难以捉摸，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、局部微电路和感官知觉的水平上研究视听时间处理的神经基础。例如，使用药理学操作，我们发现大鼠视听皮层（V2 L）中的GABA能神经传递不仅控制视听整合的精确时间，而且还影响感知绑定发生的时间窗口。也就是说，考虑到局部GABA能微电路的复杂性和皮层锥体神经元上特定位置表达的各种GABA-A受体亚单位，需要更多的工作来揭示GABA能神经传递控制视听刺激的时间整合成统一的感受器的细胞机制。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+在体电生理记录，在行为大鼠中解决以下目标：（1）确定单感觉和多感觉丘脑皮层投射到V2 L皮层如何有助于视听时间加工和感知;（2）探讨V2 L皮层GABA能中间神经元在视听时间加工和知觉中的作用;（3）确定V2 L皮质锥体神经元上表达的GABA-A受体亚单位中哪些负责精细调节视听时间加工和知觉。 最终，鉴于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能够很好地解决这个长期存在的问题：哺乳动物的大脑如何将紧密定时的听觉和视觉刺激整合到一个统一的感知中？