In CNS the oxytocin receptor (OXTR) regulates several neuroendocrine and cognitive functions. Recently, the OXTR KO mouse (OXTR-/-) has been validated as a genetic animal model for autism disorders. The impairment of cognitive flexibility shown by OXTR-/- mice suggests a deficit in spatial memory functions associable with the hippocampus. This prompted us to study whether OXTR-/- hippocampi show any synaptic alteration using primary cultures of hippocampal neurons from E18 OXTR+/+ and OXTR-/- mice. Our results show that OXTR+/+ and OXTR-/- neurons are equally capable to form synaptic-like contacts in vitro. Nevertheless, we have detected a significantly decreased expression of the pre-synaptic vesicular GABA transporter (vGAT), and of the post-synaptic scaffolding protein gephyrin. To check whether the alterations of synaptic proteins are reflected by any functional change(s) we have investigated the electrical activities of hippocampal neurons using the patch-clamp technique. Frequency and amplitude of spontaneous glutamatergic postsynaptic currents have been analyzed and compared between neurons derived from OXTR-/- and OXTR+/+ mice. Our results indicate that both amplitude and frequency were significantly higher in OXTR-/- than in OXTR+/+ neurons, in line with the increase of of VGLUT and of PSD95. All together these results show the presence of synaptic abnormalities both in terms of protein expression and electrical activity in the hippocampal neurons from OXTR-/- mice.