Altered fronto-striatal functions in the Gdi1-null mouse model of X-linked Intellectual Disability. (6th March 2017)

• Record Type: Journal Article
• Authors: Morè, Lorenzo; Künnecke, Basil; Yekhlef, Latefa; Bruns, Andreas; Marte, Antonella; Fedele, Ernesto; Bianchi, Veronica; Taverna, Stefano; Gatti, Silvia; D'Adamo, Patrizia
• Is Part Of: Neuroscience. Volume 344(2017)
• Page Start: 346
• Page End: 359
• Publication Date: 2017-03-06
• Subjects: αGDI RAB GDP dissociation inhibitor alpha -- CI conditioned inhibition -- CS conditioned stimulus -- EPSCs excitatory postsynaptic currents -- fMRI functional magnetic resonance imaging -- LI latent inhibition -- mPFC medial prefrontal cortex -- MSNs medium spiny neurons -- Pr release probability -- RRP ready releasable pool -- SV synaptic vesicles -- US unconditioned stimulus -- VTA ventral tegmental area -- XLID X-linked Intellectual Disability; X-linked Intellectual Disability -- Gdi1-null mice -- appetitive conditioning -- excitatory synapses -- fronto-striatal synaptic plasticity; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.12.043
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Attention and stimulus selection deficits in Gdi1 -null Intellectual Disability model. Behavioral deficits correlated with fronto-striatal system dysfunction. A major role for glutamatergic activity in fronto-striatal circuitry dysfunction. Correlation between reported patient's cognitive deficits and present findings. 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.