Reduced NMDA-receptor (NMDAR) function has been implicated in the 
pathophysiology of neuropsychiatric disease, most strongly in schizophrenia but 
also recently in autism spectrum disorders (ASD). To determine the direct 
contribution of NMDAR dysfunction to disease phenotypes, a mouse model with 
constitutively reduced expression of the obligatory NR1 subunit has been 
developed and extensively investigated. Adult NR1(neo-/-) mice show multiple 
abnormal behaviors, including reduced social interactions, locomotor 
hyperactivity, self-injury, deficits in prepulse inhibition (PPI) and sensory 
hypersensitivity, among others. Whereas such phenotypes have largely been 
interpreted in the context of schizophrenia, these behavioral abnormalities are 
rather non-specific and are frequently present across models of diseases 
characterized by negative symptom domains. This study investigated auditory 
electrophysiological and behavioral paradigms relevant to autism, to determine 
whether NMDAR hypofunction may be more consistent with adult ASD-like 
phenotypes. Indeed, transgenic mice showed behavioral deficits relevant to all 
core ASD symptoms, including decreased social interactions, altered ultrasonic 
vocalizations and increased repetitive behaviors. NMDAR disruption recapitulated 
clinical endophenotypes including reduced PPI, auditory-evoked response N1 
latency delay and reduced gamma synchrony. Auditory electrophysiological 
abnormalities more closely resembled those seen in clinical studies of autism 
than schizophrenia. These results suggest that NMDAR hypofunction may be 
associated with a continuum of neuropsychiatric diseases, including 
schizophrenia and autism. Neural synchrony abnormalities suggest an imbalance of 
glutamatergic and GABAergic coupling and may provide a target, along with 
behavioral phenotypes, for preclinical screening of novel therapeutics.