ALTERED FRONTO-STRIATAL FUNCTIONS IN THE GDI1-NULL MOUSE MODEL OF X-LINKED INTELLECTUAL DISABILITY

RAB-GDP dissociation inhibitor 1 (GDI1) loss-of function mutations are responsible for a form of nonspecific 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 Gdil/-null mice are impaired in attention and associative learning processes, which are a key part of the cognitive impairment observed in XLID patients. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of IBRO.