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Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked intellectual disability

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More, Lorenzo, Künnecke, Basil, Yekhlef, Latefa, Bruns, Andreas, Marte, Antonella, Fedele, Ernesto, Bianchi, Veronica, Taverna, Stefano, Gatti, Silvia and D'Adamo, Patrizia (2017) Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked intellectual disability. Neuroscience, 344 . pp. 346-359. doi:10.1016/j.neuroscience.2016.12.043

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Abstract

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.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH): Executive functions (Neuropsychology), Conditioned response, Synaptic vesicles, Learning disabilities
Journal or Publication Title: Neuroscience
Publisher: Elsevier
ISSN: 0306-4522
Official Date: 6 March 2017
Dates:
DateEvent
6 March 2017Published
3 January 2017Available
23 December 2016Accepted
Volume: 344
Page Range: pp. 346-359
DOI: 10.1016/j.neuroscience.2016.12.043
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
Funder: Fondation Téléthon, F. Hoffmann-La Roche & Co. (FHLRCo.)
Grant number: TCP04015 (Fondation Téléthon), RPF #138 (F. Hoffmann-La Roche & Co. (FHLRCo.))
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