One of the key elements to survival is the ability of our brain to recall threatening situations from the past so our self-defense mechanism can respond swiftly. Cerebellar lesion and stimulation studies in rodents and humans suggest a contribution of the cerebellum to anxiety and fear extinction behavior. However, a clear understanding of the circuitry and learning mechanisms within the cerebellum contributing to fear extinction is missing. Thus, the goal of this project is to investigate the cerebellar contribution and its intrinsic mechanisms to fear extinction in wildtype and cerebellar degenerative mouse models for episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). We will attempt to rescue fear conditioning, extinction or retrieval deficits with optogenetic, chemogenetic and pharmacological strategies in the next funding period.
Guiding questions of A21: