mTOR in Acquired and Genetic Models of Epilepsy

Mutations in genes regulating the mechanistic target of rapamycin (mTOR) signaling pathway have emerged as a common cause of childhood epilepsy, including focal cortical dysplasia, hemimegalencephaly, and tuberous sclerosis complex. Dysregulation of mTOR signaling is also implicated in nongenetic causes of epilepsy, such as following status epilepticus or traumatic brain injury. In this chapter, we describe the evidence linking the mTOR pathway to genetic and acquired epilepsies, the variety of animal models developed to examine mTOR pathway signaling in the brain, and the general patterns of brain pathology produced by pathway disruption. We also examine potential mechanisms by which disrupted mTOR signaling regulates brain development, neuronal excitability, and epileptogenesis. The variety of tissues and cellular functions regulated by mTOR, and the breadth of epilepsies linked to disrupted mTOR signaling, all implicate the pathway as an important modulator of epileptogenesis.