NMDA receptor dysfunction in autism spectrum disorders

•Human ASD-associated genetic variations are found in genes encoding NMDAR subunits.•Pharmacological enhancement or suppression of NMDARs ameliorates ASD symptoms in humans.•NMDAR dysfunction in either direction is associated with ASD-like behaviors in animals.•Correction of NMDAR dysfunction rescues ASD-like behaviors in animals.

Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDAR dysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs.