Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia?

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Reduced NMDA-receptor (NMDAR) function is implicated in schizophrenia and autism spectrum disorders (ASD).
• Mouse models are crucial for understanding the direct contribution of NMDAR dysfunction to disease phenotypes.

Purpose of the Study:

• To investigate if NMDAR hypofunction is associated with autism spectrum disorder (ASD)-like phenotypes.
• To compare the behavioral and electrophysiological abnormalities in a mouse model with those seen in clinical studies of autism and schizophrenia.

Main Methods:

• Utilized a mouse model with reduced expression of the NR1 subunit (NR1(neo-/-) mice).
• Assessed behavioral paradigms relevant to ASD, including social interaction, ultrasonic vocalizations, and repetitive behaviors.
• Conducted auditory electrophysiological tests, including prepulse inhibition (PPI) and evoked response latency.

Main Results:

• NR1(neo-/-) mice exhibited behavioral deficits consistent with core ASD symptoms.
• NMDAR disruption recapitulated clinical endophenotypes such as reduced PPI, delayed auditory evoked response N1 latency, and decreased gamma synchrony.
• Auditory electrophysiological abnormalities in mice more closely resembled those in clinical autism studies than schizophrenia studies.

Conclusions:

• NMDAR hypofunction may be associated with a continuum of neuropsychiatric diseases, including both schizophrenia and ASD.
• Neural synchrony abnormalities suggest an imbalance in glutamatergic and GABAergic signaling.
• Behavioral and neural synchrony phenotypes offer potential targets for preclinical screening of novel therapeutics.