Autism Spectrum Disorders (ASD) comprise a heterogeneous group of neuro-developmental disorders, mainly of genetic origin, characterized by impaired social interactions, communications deficits and stereotyped behaviors.

In a few cases, ASD have been found to be associated with a single mutation in genes involved in synaptic function. These include a mutation in the gene encoding for neuroligin (NL) 3 a postsynaptic adhesion molecule which together with its binding partner neuroexin bridges the synaptic cleft and ensures a corrected cross-talk between post and presynaptic specializations and the maintenance of an appropriate excitatory/inhibitory (E/I) balance. Transgenic mice carrying the human NLG3 R451C mutation constitute an ideal animal model for studying ASD since these animals exhibit impaired social interactions and enhanced spatial learning abilities reminiscent of those present in some ASD patients. In addition, these mice display an increased GABAA-mediated synaptic transmission in the forebrain.  In this study, a multidisciplinary approach (including electrophysiology, imaging, immunocytochemistry, molecular biology and behavior),will be used to verify the hypothesis that early developmental changes in GABAergic signaling in NL3 R451C KI mice affect the dynamic properties of neuronal networks and information processing in the hippocampus. Experiments performed at single cell level will allow assessing possible deficits in network activity, in the E/I balance, in GABAA receptor trafficking and lateral diffusion. Molecular biology tools will be used to identify the mechanisms determining synapse specificity of NLG3. This study will contribute to better understanding the mechanisms of ASD leading to the identification of new molecular targets useful for developing novel therapeutic tools for the cure of these devastating disorders.


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