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.
Most recent publication (click logo):
CACNA1A haploinsufficiency leads to reduced synaptic function and increased intrinsic excitability. Hommersom MP, Doorn N, Puvogel S, Lewerissa EI, Mordelt A, Ciptasari U, Kampshoff F, Dillen L, van Beusekom E, Oudakker A, Kogo N, Dolga AM, Frega M, Schubert D, van de Warrenburg BPC, Nadif Kasri N, van Bokhoven H (2024) Brain 139:16–17.
Impaired GABAergic regulation and developmental immaturity in interneurons derived from the medial ganglionic eminence in the tuberous sclerosis complex. Scheper M, Sørensen FNF, Ruffolo G, Gaeta A, Lissner LJ, Anink JJ, Korshunova I, Jansen FE, Riney K, van Hecke W, Mühlebner A, Khodosevich K, Schubert D, Palma E, Mills JD, Aronica E (2024) Acta Neuropathol 147.
SCN1A-deficient excitatory neuronal networks display mutation-specific phenotypes. Van Hugte EJH, Lewerissa EI, Wu KM, Scheefhals N, Parodi G, Van Voorst TW, Puvogel S, Kogo N, Keller JM, Frega M, Schubert D, Schelhaas HJ, Verhoeven J, Majoie M, Van Bokhoven H, Kasri NN (2023) Brain 146:5153–5167.
An in silico and in vitro human neuronal network model reveals cellular mechanisms beyond NaV1.1 underlying Dravet syndrome. Doorn N, van Hugte EJH, Ciptasari U, Mordelt A, Meijer HGE, Schubert D, Frega M, Nadif Kasri N, van Putten MJAM (2023) Stem cell reports 18:1686–1700.
Excitatory/inhibitory balance in epilepsies and neurodevelopmental disorders: Depolarizing γ-aminobutyric acid as a common mechanism. Van Hugte EJH, Schubert D, Nadif Kasri N (2023) Epilepsia 64:1975–1990.
Currently on BioRxiv
https://orcid.org/0000-0002-1202-4363