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

L Morè, B Künnecke, L Yekhlef, A Bruns, A Marte, E Fedele, V Bianchi, S Taverna, S Gatti, P D'Adamo

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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. © 2017 The Authors
Original languageEnglish
Pages (from-to)346-359
Number of pages14
Issue number5
Publication statusPublished - 2017


Cite this

Morè, L., Künnecke, B., Yekhlef, L., Bruns, A., Marte, A., Fedele, E., Bianchi, V., Taverna, S., Gatti, S., & D'Adamo, P. (2017). Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability. Neuroscience, 344(5), 346-359.