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

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.

• Authors: Lorenzo Morè, Basil Künnecke, Latefa Yekhlef, Andreas Bruns, Antonella Marte, Ernesto Fedele, Veronica Bianchi, Stefano Taverna, Silvia Gatti, Patrizia D'Adamo
• Journal: Neuroscience (Neuroscience) Vol. 344 Pg. 346-359 (03 06 2017) ISSN: 1873-7544 [Electronic] United States
• PMID: 28057534 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• GDP dissociation inhibitor 1
• Guanine Nucleotide Dissociation Inhibitors
• Dopamine

Topics

• Amygdala (diagnostic imaging, physiopathology)
• Animals
• Association Learning (physiology)
• Attention (physiology)
• Conditioning, Psychological (physiology)
• Discrimination, Psychological (physiology)
• Disease Models, Animal
• Dopamine (metabolism)
• Excitatory Postsynaptic Potentials (physiology)
• Frontal Lobe (diagnostic imaging, physiopathology)
• Guanine Nucleotide Dissociation Inhibitors (deficiency, genetics)
• Inhibition, Psychological
• Intellectual Disability (diagnostic imaging, physiopathology, psychology)
• Male
• Mice, Knockout
• Neostriatum (diagnostic imaging, physiopathology)
• Neural Pathways (diagnostic imaging, physiopathology)
• Random Allocation
• Synaptic Vesicles (metabolism)
• Time Perception (physiology)
• Tissue Culture Techniques