Hitting the Right Spot: NMDA Receptors in the Auditory Thalamus May Hold the Key to Understanding Schizophrenia

In this issue, Wang and colleagues solve an important puzzle in the understanding of schizophrenia. Previous work has linked N-methyl-D-aspartate (NMDA) receptor hypofunction to schizophrenia and shown that individuals with schizophrenia have a suppressed steady-state cortical response to 40-Hz repetitive auditory stimulation. However, systemic application of NMDA antagonists paradoxically increases this cortical response in rodents. Here, by specifically applying NMDA receptor blockade in the auditory thalamus while simultaneously measuring the acoustically driven response in 2 cortical regions, Wang and colleagues found the drop in the steady-state response that is seen in schizophrenia. These findings solve an important paradox in the field and suggest that specific thalamic neurochemical alterations may occur in the brain of individuals with schizophrenia. In addition, this work suggests that suppression of NMDA receptors in the thalamus may serve as a potential animal model for the disease.