Neuronal mechanisms underlying sensory filtering and multisensory integration

我们大脑的唯一输入是感觉信息，这些信息经过处理、存储和整合，以产生大脑的输出行为反应。我们的感官一直处于活跃状态，用感官信息轰击大脑。为了应对大量的刺激，不同的机制在感觉处理路径上过滤掉不重要的信息，从而使大脑能够保护其宝贵的资源免受冗余信息的影响，并专注于突出的和潜在的重要输入。我的研究项目集中在前注意处理阶段与感觉信息处理、过滤和整合有关的神经机制，在感觉信号到达对意识感知很重要的高级大脑结构之前。我采用组织学方法，体外和体内电生理记录，以及行为读数，结合药理学，光遗传学和化学遗传学方法，以破译神经回路和突触机制下的感觉过滤和多感觉整合。大鼠的声惊反应可以作为注意前感觉过滤和整合过程的行为解读。惊吓反应是一种反射行为，由一条非常短、描述良好的途径介导。习惯化和预脉冲抑制（PPI）是两种反映感觉过滤过程的惊吓调节。在过去的17年里，我的工作对我们目前对习惯化和PPI中涉及的神经元回路和突触机制的了解做出了重大贡献。我未来五年的目标是进一步揭示习惯化和PPI的细胞和分子机制，并将新的重点放在多感觉整合上。更具体地说，在未来五年的资助中，我将：1)在分子水平上破译介导声惊吓习惯化的同突触机制，并探索这一机制在其他感觉通路中实现的一般机制。2)利用新颖的光遗传学和化学遗传学工具，进一步建立涉及惊吓前脉冲抑制（PPI）的抑制性前馈神经回路，挑战中脑桥脚被盖是提供惊吓抑制的中心结构的长期假设。3)利用视觉和视听PPI，探索脑干水平上多感觉统合的潜在机制。该结果将为早期感觉信息处理、过滤和整合在大脑中的基本机制提供有价值的见解。这种理解对于开发能够根据其显著性或新颖性而不是其物理特性来过滤信息的技术系统也很有用。

The sole input into our brain is sensory information, which is processed, stored, and integrated in order to generate the brain's output a behavioural response. Our senses are constantly active, bombarding the brain with sensory information. In order to cope with this vast amount of stimulation, different mechanisms are in place that filter out unimportant information along the sensory processing pathways, thereby enabling the brain to protect its valuable resources from redundant information, and focus on salient and potentially important input instead. My research program focuses on the neural mechanisms concerned with sensory information processing, filtering, and integration in pre-attentive processing stages, before sensory signals reach higher brain structures that are important for a conscious percept. I employ histological approaches, electrophysiological recordings in vitro and in vivo, as well as behavioral read-outs, combined with pharmacology, optogenetic and chemogenetic approaches, in order to decipher the neural circuits and synaptic mechanisms underlying sensory filtering and multisensory integration. The acoustic startle response in rats can be used as a behavioral read out of pre-attentive sensory filtering and integration processes. The startle response is a reflective behavior mediated by a very short, well described pathway. Habituation and prepulse inhibition (PPI) are two startle modulations that reflect sensory filtering processes. Over the last 17 years, my work has contributed substantially to our current knowledge of neuronal circuits and synaptic mechanisms involved in habituation and PPI. My goal for the next five years is to further unravel the cellular and molecular mechanisms underlying habituation and PPI, with a new focus on multi-sensory integration. More specifically, in the next five years of funding I will: 1) Decipher the homosynaptic mechanism mediating habituation of acoustic startle on a molecular level and explore to what extend this mechanism is a general mechanism implemented also in other sensory pathways.2) Further establish the inhibitory feed-forward neurocircuitry involved in prepulse inhibition (PPI) of startle, challenging the long-standing hypothesis that the midbrain pedunculopontine tegmentum is the central structure providing startle inhibition, using novel and innovative optogenetic and chemogenetic tools. 3) Explore the underlying mechanisms of multisensory integration on the level of the brainstem, using visual and audiovisual PPI. The results will give valuable insights of fundamental mechanisms of early stage sensory information processing, filtering, and integration in the brain. This understanding may also be useful for developing technical systems with an ability to filter information based on their salience or novelty rather than their physical properties.