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A21 - Cerebellar contribution to fear extinction

Melanie Mark

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:

  • What regions and cell types of the cerebellum are active during the different phases of fear extinction?
  • Can we control (i. e. delay or accelerate) fear extinction from the cerebellar cortex or deep cerebellar nuclei using optogenetics?
  • How is the cerebellum involved in prediction errors during fear extinction?
  • Do our cerebellar degenerative mouse models for EA2 and SCA6 display deficits in fear conditioning, retrieval or extinction? Can we rescue these deficits in EA2 and SCA6 mice with optogenetic strategies?

Melanie Mark

Projektleiterin A21

Ruhr-Universität Bochum

Johanna Pakusch

Doktorandin A21

Ruhr-Universität Bochum

4 project relevant publications

Ernst TM, Brol AE, Gratz M, Ritter C, Bingel U, Schlamann M, Maderwald S, Quick HH, Merz CJ, Timmann D (2019) The cerebellum is involved in processing of predictions and prediction errors in a fear conditioning paradigm. eLife. 8.

Bohne P, Schwarz MK, Herlitze S, Mark MD (2019) A New Projection From the Deep Cerebellar Nuclei to the Hippocampus via the Ventrolateral and Laterodorsal Thalamus in Mice. Front Neural Circuits. 13: 51.

Eickelbeck D, Karapinar R, Jack A, Suess ST, Barzan R, Azimi Z, Surdin T, Grömmke M, Mark MD, Gerwert K, Jancke D, Wahle P, Spoida K, Herlitze S (2019) CaMello-XR enables visualization and optogenetic control of Gq/11 signals and receptor trafficking in GPCR-specific domains. Commun Biol. 2: 60.

Mark MD, Wollenweber P, Gesk A, Kösters K, Batzke K, Janoschka C, Maejima T, Han J, Deneris ES, Herlitze S (2019) RGS2 drives male aggression in mice via the serotonergic system. Commun Biol. 2(1): 1–17.