Cerebellar Fastigial Motor and Non-motor Circuits

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Project Summary DESCRIPTION (provided by applicant): The goal of this project is to provide new information about the specific brain circuits which enable us to regulate our posture, movements, and arousal levels when we are exposed to unexpected stimuli or potentially threatening conditions. Several psychiatric and neurological disorders are associated with impairments in motor tone and arousal regulation which manifest as sensory hypersensitivity, excessive startle reactivity, and increased anxiety. This research focuses on the cerebellum, a part of the brain known best for its role in coordinating movements and learning to anticipate when and how to move, but is also important for regulating wake-state arousal levels. Researchers and clinicians currently lack specific information needed to develop and target new therapeutic treatments to patients who suffer from dysregulation of defensive arousal. The specific objectives of this project are to provide anatomical, physiological, and functional information about specific cerebellar cell types which regulate movements of the trunk, head and eyes and levels of arousal via their synaptic connections with brainstem control centers. To achieve these objectives, anatomical circuit analyses will map differential synaptic connectivity of specific cerebellar neurons, neurophysiological analyses will be used to monitor activity in specific types of cerebellar neurons under conditions of spontaneous and sensory- evoked arousal, and behavioral and physiological analyses will determine the impact of manipulating activity of specific cerebellar cell types on the online and learned regulation of arousal responses to unexpected or potentially threatening stimuli. These experiments will provide a critical foundation for developing pharmacological or neurostimulation therapies for treating patients who suffer from impairments in the abiilty to regulate how they respond to unexpected threatening stimuli.