Neuroligins (NLGNs) are postsynaptic cell adhesion molecules that can induce synaptic maturation through the interaction with presynaptic adhesion molecules called Neurexins (NRXNs). In recent years, mutations, deletions and copy number variations in both NLGNs and NRXNs have been discovered in the patients with autism, indicating that impairment in synapses caused by dysfunction of these molecules may be responsible for autism. To study the relevance between these mutations and autism, we generated knock-in mice recapitulating a mutation of NLGN3 called R451C identified in patients with autism. NLGN3 R451C mice had normal locomotor activities but showed impaired social interaction and enhanced spatial learning and memory in behavioral tests, which are reminiscent of the clinical features of autism. Although numbers and structure of synapses are normal, inhibitory synaptic transmission was significantly enhanced in the pyramidal neurons in somatosensory cortex in the knock-in mice. Administration of GABA blocker, picrotoxin, ameliorated the impaired social interaction suggesting that this can be the cause of the social abnormality. On the other hand, parameters indicating impaired synaptic maturation (enhancement of NMDA/AMPA ratio, NR2B function, and LTP) were observed in CA1 hippocampal pyramidal neurons in the knock-in mice and these are likely enhancing memory ability in the mutants. We speculate that enhancement of inhibitory synaptic function in cortical neurons may also be a result of impaired synaptic maturation and this creates clinical features in some types of autism.