Epilepsy is characterized by excessive cortical neuron activity26, with multiple molecular pathways involved. For example, previous studies have implicated disruptions of synaptic modulatory pathways29 and alterations in ion channel activity30. However, how these pathways converge to contribute to the disease and whether they are cause or consequence remains largely unknown. Nuclear lncRNAs are emerging as common structures for providing activity-dependent platforms for the sophistication of functional processes in higher organisms by bringing together many cellular components into discrete functional entities. Here we provide evidence that the lncRNA NEAT1, previously suggested to be involved in human intractable seizure tissue25, contributes to the modulatory capacity of neuronal excitability and that dysregulation thereof renders neurons susceptible to seizure activity. We show that expression of NEAT1 is down-regulated in response to acute neuronal activity and binds ion channel modulatory proteins such as the potassium channel-interacting protein KCNAB2, which is itself associated with neuronal excitability17 and epilepsy19. We interpret these data to mean that NEAT1 may provide a scaffolding function in the nucleus that upon neuronal activation, releases modulatory proteins to fine-tune the excitatory response.
