Role of Rab GDP dissociation inhibitor α in regulating plasticity of hippocampal neurotransmission

Rab CDP dissociation inhibitor alpha (Rab GDl alpha) is a regulator of the Rab small G proteins implicated in neurotransmission, and mutations of Rab GDl alpha cause human X-linked mental retardation associated with epileptic seizures. In Rab GDl alpha-deficient mice, synaptic potentials in the CA1 region of the hippocampus displayed larger enhancement during repetitive stimulation, which was apparently opposite to the phenotype of Rab3A-deficient mice. Furthermore, the Rab GDl alpha-deficient mice showed hypersensitivity to bicuculline, an inducer of epileptic seizures. These results suggest that Rab GDl alpha plays a specialized role in Rab3A recycling to suppress hyperexcitability via modulation of presynaptic forms of plasticity.