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。为了科普如此大量的刺激，大脑会有不同的机制来过滤掉沿着感觉处理路径的不重要信息，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。 我的研究项目主要集中在与感官信息处理，过滤和前注意处理阶段的整合有关的神经机制，在感官信号到达对意识感知重要的高级大脑结构之前。我采用组织学方法，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的方法，以破译神经回路和突触机制的感觉过滤和多感觉整合。 大鼠的声惊吓反应可以作为前注意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，由一个非常短的，描述良好的途径介导。习惯化和前脉冲抑制（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所涉及的神经元回路和突触机制的认识做出了重大贡献。我未来五年的目标是进一步揭示习惯化和PPI背后的细胞和分子机制，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)在分子水平上解读介导听觉惊吓习惯化的同突触机制，并探索该机制在何种程度上是其他感觉通路中也实现的一般机制。 2)进一步建立参与惊吓前脉冲抑制（PPI）的抑制性前馈神经回路，挑战长期存在的假设，即中脑脚桥被盖是提供惊吓抑制的中心结构，使用新颖和创新的光遗传学和化学遗传学工具。 3)使用视觉和视听PPI探索脑干水平上多感觉整合的潜在机制。 这些结果将为大脑早期感觉信息处理、过滤和整合的基本机制提供有价值的见解。这种理解也可能有助于开发技术系统，使其能够根据信息的突出性或新奇而不是其物理特性来过滤信息。

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.