Department of Molecular and Integrative Physiology, University of Illinois, Urbana-Champaign, Illinois.
Beckman Institute for Advanced Science and Technology, Urbana, Illinois.
Int J Neuropsychopharmacol. 2020 Dec 3;23(9):578-580. doi: 10.1093/ijnp/pyaa032.
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.
在本期中，Wang 及其同事解决了精神分裂症理解中的一个重要难题。先前的工作将 N-甲基-D-天冬氨酸 (NMDA) 受体功能低下与精神分裂症联系起来，并表明精神分裂症患者对 40Hz 重复听觉刺激的稳态皮质反应受到抑制。然而，NMDA 拮抗剂的全身应用在啮齿动物中反而会增加这种皮质反应。在这里，Wang 及其同事通过在听觉丘脑特异性应用 NMDA 受体阻断剂，同时测量 2 个皮质区域的声驱动反应，发现了精神分裂症患者中观察到的稳态反应下降。这些发现解决了该领域的一个重要悖论，并表明特定的丘脑神经化学改变可能发生在精神分裂症患者的大脑中。此外，这项工作表明，丘脑 NMDA 受体的抑制可能作为该疾病的潜在动物模型。
