Vice speaker of the Research Department of Neuroscience
Workgroup Behavioral Neurobiology
Faculty of Biology and Biotechnology
Ruhr University Bochum
Universitätsstr. 150
44801 Bochum
Room:
ND 7/33
Phone:
+49 (0)234 32-27913
Email:
melanie.mark@ruhr-uni-bochum.de
The main focus of my group is to understand the role of the cerebellum in diseased disorders, such as ataxia, stress induced dystonia and absence epilepsy. I created transgenic mouse models representing the human diseases Episodic Ataxia type 2 and Spinocerebellar Ataxia type 6 to aid in understanding the contribution of the cerebellum to these diseased states. Unfortunately, individuals suffering from ataxia have no means of therapeutic relief. Using our mouse models, we hope to identify second messenger pathways and specific neurons in the cerebellum involved in these diseased states, in order to identify more effective therapeutic tools either pharmacological, optogenetic or genetic to help affected individuals.
Another interest is the serotonergic system and how it regulates aggression. We asked ourselves: Why are some individuals more aggressive than others? Is it due to their environment or are they just born this way? To address these questions, we created 2 mouse models, one overexpressing RGS2 (regulators of G protein signaling) specifically in serotonergic neurons and another mouse line where we knocked out the P/Q type calcium channel specifically in serotonergic neurons. Interestingly, both lines display aggressive behavior without altering anxiety levels. The main objective of this project is to identify molecules and their pathways, which modulate aggression via the serotonergic system.
Lastly, we are interested in how the cerebellum contributes to cognitive functions such as fear and anxiety. Traditionally the cerebellum was thought to be involved in only motor function and learning, however there is growing evidence supporting its role in emotional behaviors such as fear. We will use a combination of transgenic mouse models and pharmacological and optogenetic tools to identify specific cerebellar regions/neurons and the second messengers which are important for fear conditioning.
Schwitalla, J. C., Pakusch, J., Mücher, B., Brückner, A., Depke, D. A., Fenzl, T., De Zeeuw, C. I., Kros, L., Hoebeek, F. E. & Mark, M. D. (2022). Controlling absence seizures from the cerebellar nuclei via activation of the Gq signaling pathway. Cellular and Molecular Life Sciences, 79(4). https://doi.org/10.1007/s00018-022-04221-5
Karapinar, R., Schwitalla, J. C., Eickelbeck, D., Pakusch, J., Mücher, B., Grömmke, M., Surdin, T., Knöpfel, T., Mark, M. D., Siveke, I. & Herlitze, S. (2021). Reverse optogenetics of G protein signaling by zebrafish non-visual opsin Opn7b for synchronization of neuronal networks. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-24718-0
Miao, Q., Herlitze, S., Mark, M. D. & Noebels, J. L. (2020). Adult loss of Cacna1a in mice recapitulates childhood absence epilepsy by distinct thalamic bursting mechanisms. Brain, 143(1), 161–174. https://doi.org/10.1093/brain/awz365
Fekete, A., Nakamura, Y., Yang, Y. M., Herlitze, S., Mark, M. D., DiGregorio, D. A. & Wang, L. (2019). Underpinning heterogeneity in synaptic transmission by presynaptic ensembles of distinct morphological modules. Nature Communications, 10(1). https://doi.org/10.1038/s41467-019-08452-2
Spoida, K., Eickelbeck, D., Karapinar, R., Eckhardt, T., Mark, M. D., Jancke, D., Ehinger, B. V., König, P., Dalkara, D., Herlitze, S. & Masseck, O. A. (2016). Melanopsin Variants as Intrinsic Optogenetic On and Off Switches for Transient versus Sustained Activation of G Protein Pathways. Current Biology, 26(9), 1206–1212. https://doi.org/10.1016/j.cub.2016.03.007
Mark, M. D., Krause, M., Boele, H., Kruse, W., Pollok, S., Kuner, T., Dalkara, D., Koekkoek, S. K. E., De Zeeuw, C. I. & Herlitze, S. (2015). Spinocerebellar Ataxia Type 6 Protein Aggregates Cause Deficits in Motor Learning and Cerebellar Plasticity. The Journal of Neuroscience, 35(23), 8882–8895. https://doi.org/10.1523/jneurosci.0891-15.2015
Maejima, T., Wollenweber, P., Teusner, L. U. C., Noebels, J. L., Herlitze, S. & Mark, M. D. (2013). Postnatal Loss of P/Q-Type Channels Confined to Rhombic-Lip-Derived Neurons Alters Synaptic Transmission at the Parallel Fiber to Purkinje Cell Synapse and Replicates GenomicCacna1aMutation Phenotype of Ataxia and Seizures in Mice. The Journal of Neuroscience, 33(12), 5162–5174. https://doi.org/10.1523/jneurosci.5442-12.2013
Mark, M. D., Maejima, T., Kuckelsberg, D., Yoo, J. S., Hyde, R., Shah, V. N., Gutierrez, D. V., Moreno, R. E. V., Kruse, W., Noebels, J. L. & Herlitze, S. (2011). Delayed Postnatal Loss of P/Q-Type Calcium Channels Recapitulates the Absence Epilepsy, Dyskinesia, and Ataxia Phenotypes of Genomic Cacna1A Mutations. The Journal of Neuroscience, 31(11), 4311–4326. https://doi.org/10.1523/jneurosci.5342-10.2011
Han, J., Mark, M. D., Li, X., Xie, M., Waka, S., Rettig, J. & Herlitze, S. (2006). RGS2 Determines Short-Term Synaptic Plasticity in Hippocampal Neurons by Regulating Gi/o- Mediated Inhibition of Presynaptic Ca2+ Channels. Neuron, 51(5), 575–586. https://doi.org/10.1016/j.neuron.2006.07.012
Li, X., Gutierrez, D. V., Hanson, M. G., Han, J., Mark, M. D., Chiel, H., Hegemann, P., Landmesser, L. T., & Herlitze, S. (2005). Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin. Proceedings of the National Academy of Sciences, 102(49), 17816–17821. https://doi.org/10.1073/pnas.0509030102
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