Euchromatin histone methyltransferase 1 regulates cortical neuronal network development
| Autor: | Nael Nadif Kasri, Monica Frega, Marco Benevento, Paul H. E. Tiesinga, Jessica Classen, Dirk Schubert, Hans van Bokhoven, Elske Bijvank, Marijn B. Martens, Lisa Epping |
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| Rok vydání: | 2016 |
| Předmět: |
Heart Defects
Congenital Neuroinformatics 0301 basic medicine Patch-Clamp Techniques Euchromatin Neurogenesis Action Potentials Haploinsufficiency Biology Article Craniofacial Abnormalities Mice 03 medical and health sciences EHMT1 Bursting 0302 clinical medicine Neurodevelopmental disorder Intellectual Disability medicine Biological neural network Animals Humans Cells Cultured Kleefstra Syndrome Cerebral Cortex Mice Knockout Genetics Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] Multidisciplinary Excitatory Postsynaptic Potentials Histone-Lysine N-Methyltransferase Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] medicine.disease Rats 030104 developmental biology Histone methyltransferase Excitatory postsynaptic potential Chromosome Deletion Nerve Net Chromosomes Human Pair 9 Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, 6 Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Heterozygous mutations or deletions in the human Euchromatin histone methyltransferase 1 (EHMT1) gene cause Kleefstra syndrome, a neurodevelopmental disorder that is characterized by autistic-like features and severe intellectual disability (ID). Neurodevelopmental disorders including ID and autism may be related to deficits in activity-dependent wiring of brain circuits during development. Although Kleefstra syndrome has been associated with dendritic and synaptic defects in mice and Drosophila, little is known about the role of EHMT1 in the development of cortical neuronal networks. Here we used micro-electrode arrays and whole-cell patch-clamp recordings to investigate the impact of EHMT1 deficiency at the network and single cell level. We show that EHMT1 deficiency impaired neural network activity during the transition from uncorrelated background action potential firing to synchronized network bursting. Spontaneous bursting and excitatory synaptic currents were transiently reduced, whereas miniature excitatory postsynaptic currents were not affected. Finally, we show that loss of function of EHMT1 ultimately resulted in less regular network bursting patterns later in development. These data suggest that the developmental impairments observed in EHMT1-deficient networks may result in a temporal misalignment between activity-dependent developmental processes thereby contributing to the pathophysiology of Kleefstra syndrome. |
| Databáze: | OpenAIRE |
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