Neuronal mechanisms underlying sensory filtering and multisensory integration

我们大脑的唯一输入是感觉信息，这些信息被处理、存储和整合，以便产生大脑的输出--行为反应。我们的感官一直处于活跃状态，用感官信息轰炸大脑。为了应对如此巨大的刺激量，不同的机制被到位，过滤掉感觉处理路径上的不重要信息，从而使大脑能够保护其宝贵的资源不受冗余信息的影响，转而专注于显著的和潜在的重要输入。 我的研究项目侧重于与前注意处理阶段的感觉信息处理、过滤和整合有关的神经机制，在感觉信号到达对意识感知至关重要的高级大脑结构之前。我使用组织学方法、体外和体内的电生理记录以及行为读出，结合药理学、光遗传学和化学遗传学方法，以破译感觉过滤和多感觉整合背后的神经回路和突触机制。 大鼠的声学惊吓反应可以作为预先注意的感觉过滤和整合过程的行为读出。惊吓反应是一种反射行为，由一条非常短的、描述得很好的途径介导。习惯化和脉冲前抑制(PPI)是反映感觉过滤过程的两种惊吓调制。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很大贡献。我未来五年的目标是进一步解开习惯化和PPI背后的细胞和分子机制，将新的重点放在多感觉整合上。更具体地说，在未来五年的拨款中，我会： 1)从分子水平上破译同源突触调节声惊厥习惯化的机制，并探讨这一机制在多大程度上是一种普遍的机制，也适用于其他感觉通路。 2)利用新颖的光遗传学和化学遗传学工具，进一步建立了惊厥前脉冲抑制(PPI)相关的抑制性前馈神经回路，挑战了长期以来关于中脑脚桥被盖是提供惊厥抑制的中枢结构的假说。 3)利用视觉和视听PPI在脑干水平上探索多感觉整合的潜在机制。 这些结果将为早期感觉信息处理、过滤和大脑整合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信息的突出程度或新颖性而不是其物理属性来过滤信息的技术系统也是有用的。

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.