Down-regulation of RalBP1 expression reduces seizure threshold and synaptic inhibition in mice.

摘要: Idiopathic epilepsy is characterized by seizures without a clear etiology and believed to have strong genetic component but exhibits complex inheritance pattern. Genetic factors seem confer low seizure threshold susceptible individuals thereby enhance epileptogenesis. However, the identity of susceptibility genes mechanisms regulating are still poorly understood. Here, we describe that reduced expression RalBP1, downstream effector small GTPases RalA RalB, lowers in mice. The intraperitoneal injection chemoconvulsant pentylenetetrazol induced more severe RalBP1 hypomorphic mice than their wild-type littermates. reduction brain has no effect on neuronal excitability, does decrease inhibitory synaptic transmission onto CA1 pyramidal neurons. This impaired inhibition was associated with loss GABAergic interneurons subfield hippocampus. present study identifies as gene provides direct evidence for role vivo.