| First Author | Bülow P | Year | 2019 |
| Journal | Cell Rep | Volume | 26 |
| Issue | 6 | Pages | 1378-1388.e3 |
| PubMed ID | 30726724 | Mgi Jnum | J:290874 |
| Mgi Id | MGI:6432007 | Doi | 10.1016/j.celrep.2019.01.035 |
| Citation | Bulow P, et al. (2019) Homeostatic Intrinsic Plasticity Is Functionally Altered in Fmr1 KO Cortical Neurons. Cell Rep 26(6):1378-1388.e3 |
| abstractText | 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. |
