Cognitive impairment in Gdi1-deficient mice is associated with altered synaptic vesicle pools and short-term synaptic plasticity, and can be corrected by appropriate learning training.

The GDI1 gene, responsible in human for X-linked non-specific mental retardation, encodes alphaGDI, a regulatory protein common to all GTPases of the Rab family. Its alteration, leading to membrane accumulation of different Rab GTPases, may affect multiple steps in neuronal intracellular traffic. Using electron microscopy and electrophysiology, we now report that lack of alphaGDI impairs several steps in synaptic vesicle (SV) biogenesis and recycling in the hippocampus.