Dirk Schubert Lab of Cellular NeuroPhysiology
Schubert Neurolab @ Cognitive Neuroscience Department, Donders Institute for Brain Cognition & Behavior
Radboudumc Nijmegen, The Netherlands
© 2021 | Impressum: Dirk Schubert, CNS Dept radboudumc, Nijmegen, The Netherlands
The main research interest of our group is the investigation of structural and functional (re)organization of cortical networks in health and disease.
The scaffold of proper structural and functional organization of the neuronal networks depends on the activity of a multitude of different transcription factors, growth factors and neuromodulators during brain development.
Many neurological disorders and their related cortical dysfunctions can be linked with abnormal activity of one or more factors or neuromodulators - be it because of genetic variations or because of pharmacological modulation during critical periods of brain development.
In our group, we are currently focussing on the structural and functional organization and maturation of excitatory (glutamatergic) and inhibitory (GABAergic) neural networks with the four translational links:
- The role of the neuromodulator serotonin and stress on the development of excitatory/inhibitory circuitry in the rodent brain.
- Epigenetic factors and neuronal network formation in models systems (rodent & human) for intellectual disability and schizophrenia.
- mTORopathies and deregulated GABA signaling in developmental epilepsy.
For our research we combine genetic editing (CRISPR/Cas), molecular, neuroanatomical, electrophysiological in vitro techniques (from single cell patch clamp over paired recordings to multielectrode array recordings), with optical stimulation (optogenetics), modelling as well as behavioural approaches, partially via intense collaborations with other research groups.
To this end in our group we have a particular focus on using human induced pluripotent stem cell (hIPSC) derived neuronal networks.c
Most recent publication (click logo):
Brunner syndrome associated MAOA mutations result in NMDAR hyperfunction and increased network activity in human dopaminergic neurons. van Rhijn J-R, Shi Y, Bormann M, Mossink B,
Frega M, Recaioglu H, Hakobjan M, Klein Gunnewiek T, Schoenmaker C, Palmer E,
Faivre L, Kittel-Schneider S, Schubert D, Brunner H, Franke B, Nadif Kasri N.
2022. Neurobiol Dis
SETD1A Mediated H3K4 Methylation and Its Role in Neurodevelopmental and Neuropsychiatric Disorders. Wang S, Bleeck A, Nadif Kasri N, Kleefstra T, van Rhijn JR, Schubert D. 2021. . Front Mol Neurosci 14. doi:10.3389/FNMOL.2021.772000
Human neuronal networks on micro-electrode arrays are a highly robust tool to study disease-specific genotype-phenotype correlations in vitro. Mossink B, Verboven AHA, van Hugte EJH, Klein Gunnewiek TM, Parodi G, Linda K, Schoenmaker C, Kleefstra T, Kozicz T, van Bokhoven H, Schubert D, Nadif Kasri N, Frega M. (2021) Stem Cell Reports. 2021 Jul 13:S2213-6711(21)00326-X. doi: 10.1016/j.stemcr.2021.07.001. Epub ahead of print. PMID: 34329594.
Imbalanced autophagy causes synaptic deficits in a human model for neurodevelopmental disorders. Linda K, Lewerissa EI, Verboven AHA, Gabriele M, Frega M, Klein Gunnewiek TM, Devilee L, Ulferts E, Hommersom M, Oudakker A, Schoenmaker C, van Bokhoven H, Schubert D, Testa G, Koolen DA, de Vries BBA, Nadif Kasri N. (2021) Autophagy. 2021 Jul 21:1-20. doi: 10.1080/15548627.2021.1936777. Epub ahead of print. PMID: 34286667.
Cadherin-13 is a critical regulator of GABAergic modulation in human stem cell derived neuronal networks. Mossink B, van Rhijn J-R, Shan Wang S,..., Schubert D†, Nadif Kasri†. (2021) Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01117-x. †Authors contributed equally to this work
Educational movie: Koolen-de Vries Syndrome
Now on bioRxiv (PrePrint):
S. Wang, J-R. van Rhijn, I. Akkouh, N. Kogo, N. Maas, A. Bleeck, E. Lewerissa, K.M. Wu, C. Schoenmaker, S. Djurovic, H. van Bokhoven, T. Kleefstra, N. Nadif Kasri, D. Schubert Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through cAMP/PKA pathway. bioRxiv 2021.05.25.445613