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A21 - Der Einfluss des Cerebellums auf die Furchtextinktion

Melanie Mark

Die Fahigkeit des Gehirns eine Situation mit einer Emotion zu verbinden und in Zukunft ahnliche Situationen anhand der alten Erfahrung zu bewerten, ist ein wichtiger Mechanismus, um das Uberleben zu sichern. Dem Cerebellum wurde in der Vergangenheit in diesem Forschungsfeld nur wenig Beachtung geschenkt. Ziel dieses Projektes ist es daher, die Beteiligung des Cerebellums und seine intrinsischen Mechanismen, welche zur Angstkonditionierung und Extinktion beitragen zu untersuchen. Diese sollen in Wildtypmausen und Mausmodellen fur Episodische Ataxie Typ 2 (EA2) und Spinocerebellare Ataxie Typ 6 (SCA6) untersucht werden. Diese krankheitsbedingten Defizite auf optogenetischem, chemogenetischem oder pharmakologischem Wege zu beheben, mochten wir uns als Ziel fur die nachste Forderperiode setzen.

Leitfragen des Projekts A21:

  • Welche Regionen und Zelltypen des Kleinhirns sind während der verschiedenen Phasen der Furchtauslöschung aktiv?
  •  Können wir die Furchtlöschung von der Kleinhirnrinde oder den tiefen Kleinhirnkernen aus mit Hilfe der Optogenetik steuern (d.h. verzögern oder beschleunigen)?
  •  Wie ist das Kleinhirn an Vorhersagefehlern während der Furchtauslöschung beteiligt?
  • Zeigen unsere degenerativen Kleinhirn-Mausmodelle für EA2 und SCA6 Defizite bei der Furchtkonditionierung, dem Abruf oder der Extinktion? Können wir diese Defizite in EA2- und SCA6-Mäusen mit optogenetischen Strategien beheben?
Zurück zur Projektübersicht

Melanie Mark

Projektleiterin A21

Ruhr-Universität Bochum

Tejas Nair

Doktorand A21

Ruhr-Universität Bochum

10 projektrelevante Publikationen

Batsikadze G*, Pakusch J*, Klein M, Ernst TM, Thieme A, Nicksirat SA, Steiner KM, Nio E, Genç E, Maderwald S, Deuschl C, Merz CJ, Quick HH, Mark MD*, Timmann D*. (2024) Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration. eNeuro. Feb 26;11(2): ENEURO.0365-23.2023. https://doi.org/10.1523/ENEURO.0365-23.2023

Bihorac J, Salem Y, Lückemann L, Schedlowski M, Doenlen R, Engler H, Mark MD, Dombrowski K, Spoida K, Hadamitzky M. (2024) Investigations on the ability of the insular cortex to process peripheral immunosuppression. Journal of Neuroimmune Pharmacology. Jul 30;19(1):40. https://doi.org/10.1007/s11481-024-10143-9

Bohne P, Josten M, Rambuscheck L, Zhu XR, Rybarski MO, Mark MD (2023) Cerebellar α1D-adrenergic receptors mediate stress-induced dystonia in totteringtg/tg mice. bioRxiv11.12.566757. https://doi.org/10.1101/2023.11.12.566757

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. https://doi.org/10.3389/fncir.2019.00051

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:e46831. https://doi.org/10.7554/eLife.46831

Karapinar R# , Schwitalla JC# , Eickelbeck D# , Pakusch J, Mücher B, Grömmke M, Surdin T, Knöpfel T, Mark MD*, Siveke I, Herlitze S* (2021) Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks. Nature Commun. Jul 23;12(1):4488. *Equal corresponding author. https://doi.org/10.1038/s41467-021-24718-0

Mark M, Pakusch J, Ernst TM, Timmann D (2022). Cerebellum and Emotion Memory. In: Adamaszek, M., Manto, M., Schutter, D.J.L.G. (eds) The Emotional Cerebellum. Advances in Experimental Medicine and Biology, vol 1378. Springer, Cham. https://doi.org/10.1007/978-3-030-99550-8_5

Nio E, Pais Pereira P, Diekmann N, Petrenko M, Doubliez A, Ernst TM, Batsikadze G, Maderwald S, Deuschl C, Üngör M, Cheng S, Merz CJ, Quick HH, Timmann D (2025) Human cerebellum and ventral tegmental area interact during extinction of learned fear. eLife 14:RP105399. https://doi.org/10.7554/eLife.105399

Piotrowski D, Clemensson EKH, Nguyen HP, Mark MD. (2024) Phenotypic analysis of ataxia in spinocerebellar ataxia type 6 mice using DeepLabCut. Sci Rep. 14:8571. https://doi.org/10.1038/s41598-024-59187-0

Surdin T, Preissing B, Rohr L, Grömmke M, Böke H, Barcik M, Zohre A, Jancke D, Herlitze S, Mark MD, Siveke I (2023) Optogenetic activation of mGluR1 signaling in the cerebellum induces synaptic plasticity. iScience. 26:105828. https://doi.org/10.1016/j.isci.2022.105828

New Year, New Me: The Facts

As the calendar turns to a new year, millions of people around the world commit to New Year’s resolutions, making promises to use the new year as a fresh beginning and an opportunity for transformation. In 2024, almost three-quarters of the British population set themselves New Year’s resolutions — that’s around 40 million people (or the entire population of Canada). This tradition was particularly strong among younger generations, with 96% of Generation Z (aged 18-27) planning resolutions, compared to just 35% of the Silent Generation (aged 79+).

Most common new years resolutions:

  1. Saving more money (52%)
  2. Eat healthier (50%)
  3. Exercise more (48%)
  4. Lose weight (37%)
  5. Spend more time with family/friends (35%)

How long do most resolutions normally last before being broken?

  • Data from America (2016) shows that 75% of individuals maintain their resolutions through the first week. 
  • 64% of individuals maintain their resolutions through the first month. 
  • 46% of individuals in America keep their resolutions past the 6-month mark.

What makes resolutions stick?

Oscarsson et al. (2020) conducted research into what makes New Year’s resolutions stick. Biggest success rates depended on how people phrased their goals. Participants who set approach-oriented goals (trying to move toward or maintain a desirable outcome or state) than those with avoidance-oriented goals (trying to move toward or maintain a desirable outcome or state) were significantly more successful (58.9% vs. 47.1%) at sticking to their goals.

The study also investigates the effects of outside support. These participants received monthly follow-ups and emails with information and exercises for coping with hurdles when striving toward personal goals, and were also encouraged to set goals using the SMART technique and to set interim goals. The group that received some support was exclusively and significantly more successful compared to the groups who received a lot of support or no support at all. 

Additionally, you might feel more successful if you set goals that are measurable in numbers. While success for a person striving to quit smoking or lose weight could easily be measured in the number of cigarettes smoked or body mass index, the success for a person striving to „take better care of themselves“ could be highly subjective and possibly impossible to measure.

So as we enter 2026, let’s remember to work with our brain’s natural learning system: Frame your goals positively, break them into manageable steps, and celebrate small wins along the way.