Homeostatic Intrinsic Plasticity Is Functionally Altered in Fmr1 KO Cortical Neurons
| Autor: | T. J. Murphy, Pernille Bülow, Gary J. Bassell, Peter Wenner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Nervous system Male congenital hereditary and neonatal diseases and abnormalities Sensory system Biology General Biochemistry Genetics and Molecular Biology Intrinsic plasticity Article Membrane Potentials 03 medical and health sciences Fragile X Mental Retardation Protein Mice 0302 clinical medicine medicine Animals Homeostasis lcsh:QH301-705.5 Ion channel Cerebral Cortex Neurons Neuronal Plasticity Cortical neurons medicine.disease FMR1 Fragile X syndrome Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Fragile X Syndrome Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 26, Iss 6, Pp 1378-1388.e3 (2019) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY Cortical hyperexcitability is a hallmark of fragile X syndrome (FXS). In the Fmr1 knockout (KO) mouse model of FXS, cortical hyperexcitability is linked to sensory hypersensitivity and seizure susceptibility. It remains unclear why homeostatic mechanisms fail to prevent such activity. Homeostatic intrinsic plasticity (HIP) adjusts membrane excitability through regulation of ion channels to maintain activity levels following activity perturbation. Despite the critical role of HIP in the maturation of excitability, it has not been examined in FXS. Here, we demonstrate that HIP does not operate normally in a disease model, FXS. HIP was either lost or exaggerated in two distinct neuronal populations from Fmr1 KO cortical cultures. In addition, we have identified a mechanism for homeostatic intrinsic plasticity. Compromising HIP function during development could leave cortical neurons in the FXS nervous system vulnerable to hyperexcitability. Graphical Abstract In Brief Fragile X syndrome (FXS) is characterized by cortical hyperexcitability, but the mechanisms driving hyperexcitability are poorly understood. Homeostatic intrinsic plasticity (HIP) regulates ion channel function to maintain appropriate activity levels. Bülow et al. show that HIP is functionally altered in FXS neurons, which may leave cortical neurons vulnerable to hyperexcitability. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|