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

Research output: Contribution to journalArticle

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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. 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
JournalNeuroscience
Volume344
Issue number5
DOIs
Publication statusPublished - 2017

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Corpus Striatum
Intellectual Disability
Learning
Neuronal Plasticity
Aptitude
Synaptic Vesicles
Executive Function
Memory Disorders
Hippocampus
Mutation
GDP dissociation inhibitor 1
Cognitive Dysfunction

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Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability. / Morè, L; Künnecke, B; Yekhlef, L; Bruns, A; Marte, A; Fedele, E; Bianchi, V; Taverna, S; Gatti, S; D'Adamo, P.

In: Neuroscience, Vol. 344, No. 5, 2017, p. 346-359.

Research output: Contribution to journalArticle

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, vol. 344, no. 5, pp. 346-359. https://doi.org/10.1016/j.neuroscience.2016.12.043
Morè, L ; Künnecke, B ; Yekhlef, L ; Bruns, A ; Marte, A ; Fedele, E ; Bianchi, V ; Taverna, S ; Gatti, S ; D'Adamo, P. / Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability. In: Neuroscience. 2017 ; Vol. 344, No. 5. pp. 346-359.
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