Altered fronto-striatal functions in the Gdi1 -null mouse model of X-linked Intellectual Disability

More, Lorenzo orcid iconORCID: 0000-0003-1156-2861, Künnecke, Basil, Yekhlef, Latefa, Bruns, Andreas, Marte, Antonella, Fedele, Ernesto, Bianchi, Veronica, Taverna, Stefano, Gatti, Silvia et al (2017) Altered fronto-striatal functions in the Gdi1 -null mouse model of X-linked Intellectual Disability. Neuroscience, 344 . pp. 346-359. ISSN 0306-4522

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RAB-GDP dissociation inhibitor 1 (GDI1) loss-of-function mutations are responsible for a form of non-specific X-linked Intellectual Disability (XLID) where the only clinical feature is cognitive impairment. GDI1 patients are impaired in specific aspects of executive functions and conditioned response, which are controlled by fronto-striatal circuitries. Previous molecular and behavioral characterization of the Gdi1-null mouse revealed alterations in the total number/distribution of hippocampal and cortical synaptic vesicles as well as hippocampal short-term synaptic plasticity, and memory deficits. In this study, we employed cognitive protocols with high translational validity to human condition that target the functionality of cortico-striatal circuitry such as attention and stimulus selection ability with progressive degree of complexity. We previously showed that Gdi1-null mice are impaired in some hippocampus-dependent forms of associative learning assessed by aversive procedures. Here, using appetitive-conditioning procedures we further investigated associative learning deficits sustained by the fronto-striatal system.

We report that Gdi1-null mice are impaired in attention and associative learning processes, which are a key part of the cognitive impairment observed in XLID patients.

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