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。

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.