Single-Cell and Neuronal Network Alterations in an In Vitro Model of Fragile X Syndrome
| Autor: | Winnok H. De Vos, Michele Giugliano, Peter Verstraelen, F Kooy, Sebastiaan Van De Vijver, Anastasiya Moskalyuk |
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| Rok vydání: | 2019 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Cognitive Neuroscience Models Neurological fragile X Biology Settore BIO/09 - Fisiologia Fragile X Mental Retardation Protein 03 medical and health sciences Cellular and Molecular Neuroscience Glutamatergic 0302 clinical medicine Neural Pathways medicine Biological neural network Animals spontaneous activity 030304 developmental biology Cerebral Cortex Mice Knockout Neurons 0303 health sciences patch-clamp medicine.disease Phenotype Mice Inbred C57BL Fragile X syndrome Electrophysiology microelectrode arrays Fragile X Syndrome Knockout mouse Excitatory postsynaptic potential network bursts GABAergic Female Neural Networks Computer Human medicine Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cerebral cortex Cerebral Cortex |
| ISSN: | 1460-2199 1047-3211 |
| Popis: | The Fragile X mental retardation protein (FMRP) is involved in many cellular processes and it regulates synaptic and network development in neurons. Its absence is known to lead to intellectual disability, with a wide range of comorbidities including autism. Over the past decades, FMRP research focused on abnormalities both in glutamatergic and GABAergic signaling, and an altered balance between excitation and inhibition has been hypothesized to underlie the clinical consequences of absence of the protein. Using Fmrp knockout mice, we studied an in vitro model of cortical microcircuitry and observed that the loss of FMRP largely affected the electrophysiological correlates of network development and maturation but caused less alterations in single-cell phenotypes. The loss of FMRP also caused a structural increase in the number of excitatory synaptic terminals. Using a mathematical model, we demonstrated that the combination of an increased excitation and reduced inhibition describes best our experimental observations during the ex vivo formation of the network connections. |
| Databáze: | OpenAIRE |
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