Serotonin in seizures and epilepsy: a neurodevelopmental perspective

The term epilepsy refers to a diverse group of disorders of different origin, which are all characterized by the repeated occurrence of transitory and localized outbursts of electrical activity, known as seizures. Several forms of epilepsy have a clear neurodevelopmental origin, due to congenital brain malformations, altered neurotransmission, or defects in maturation and plasticity of neuronal networks. A role for serotonin (5-hydroxytryptamine, 5-HT) in epilepsy has long been proposed, and classical pharmacological studies provided contrasting evidences about the 5-HT receptor pathways involved in epilepsy, supporting both a pro- and an antiepileptic action of 5-HT. More recently, work performed on mice lacking genes involved in 5-HT neuron differentiation showed that an altered development of 5-HT circuits markedly affects neuronal activity in postnatal life, indicating a protective role of 5-HT against hyperexcitability. In this chapter, we will review the major developmental perturbations of 5-HT innervation affecting neuronal excitability and seizure susceptibility.