Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at cortico-lateral amygdala synaptic connections
PLoS ONE. 2012-01-23; 7(1): e29763
DOI: 10.1371/journal.pone.0029763
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1. PLoS One. 2012;7(1):e29763. doi: 10.1371/journal.pone.0029763. Epub 2012 Jan 23.
Forebrain deletion of αGDI in adult mice worsens the pre-synaptic deficit at
cortico-lateral amygdala synaptic connections.
Bianchi V(1), Gambino F, Muzio L, Toniolo D, Humeau Y, D’Adamo P.
Author information:
(1)Dulbecco Telethon Institute at Division of Neuroscience, San Raffaele
Scientific Institute, Milan, Italy.
The GDI1 gene encodes αGDI, which retrieves inactive GDP-bound RAB from membranes
to form a cytosolic pool awaiting vesicular release. Mutations in GDI1 are
responsible for X-linked Intellectual Disability. Characterization of the
Gdi1-null mice has revealed alterations in the total number and distribution of
hippocampal and cortical synaptic vesicles, hippocampal short-term synaptic
plasticity and specific short-term memory deficits in adult mice, which are
possibly caused by alterations of different synaptic vesicle recycling pathways
controlled by several RAB GTPases. However, interpretation of these studies is
complicated by the complete ablation of Gdi1 in all cells in the brain throughout
development. In this study, we generated conditionally gene-targeted mice in
which the knockout of Gdi1 is restricted to the forebrain, hippocampus, cortex
and amygdala and occurs only during postnatal development. Adult mutant mice
reproduce the short-term memory deficit previously reported in Gdi1-null mice.
Surprisingly, the delayed ablation of Gdi1 worsens the pre-synaptic phenotype at
cortico-amygdala synaptic connections compared to Gdi1-null mice. These results
suggest a pivotal role of αGDI via specific RAB GTPases acting specifically in
forebrain regions at the pre-synaptic sites involved in memory formation.
DOI: 10.1371/journal.pone.0029763
PMCID: PMC3264564
PMID: 22291894 [Indexed for MEDLINE]