Grant: Discovery Grants Program - Individual

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.