Chapter 73 - Epilepsy in Models of Rett Syndrome

Abstract

Mutations of the gene encoding methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome, a developmental neurological condition that affects primarily females. Rett syndrome patients are affected by a host of comorbidities, with some form of epilepsy observed in approximately two-thirds of patients. At present, the mechanisms through which the absence of MeCP2 leads to network hyperexcitability and spontaneous discharges remain poorly understood. Several lines of Rett syndrome mouse models have been developed to facilitate investigations in this area, and recent results confirm the presence of hyperexcitable neural networks and spontaneous epileptiform-like discharge activities in different brain regions of these mice. This chapter will review the types of discharge activity reported in different lines of mice lacking MeCP2 either ubiquitously, regionally, or in specific neural cell lineages. Recent data suggesting mechanisms for the genesis of discharge activity, as well as model limitations, will also be discussed.