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

Neuroscience. 2017 Mar 6;344:346-359. doi: 10.1016/j.neuroscience.2016.12.043. Epub 2017 Jan 3.


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.

Keywords: Gdi1-null mice; X-linked Intellectual Disability; appetitive conditioning; excitatory synapses; fronto-striatal synaptic plasticity.

MeSH terms

  • Amygdala / diagnostic imaging
  • Amygdala / 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
  • Frontal Lobe / physiopathology*
  • Guanine Nucleotide Dissociation Inhibitors / deficiency*
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Inhibition, Psychological
  • Intellectual Disability / diagnostic imaging
  • Intellectual Disability / physiopathology*
  • Intellectual Disability / psychology
  • Male
  • Mice, Knockout
  • Neostriatum / diagnostic imaging
  • Neostriatum / physiopathology*
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Random Allocation
  • Synaptic Vesicles / metabolism
  • Time Perception / physiology
  • Tissue Culture Techniques


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