Cognitive and Auditory Neuroscience Laboratory, Institute of Neuroscience of Castilla y León (INCYL), Salamanca, Spain.
The Salamanca Institute for Biomedical Research (IBSAL), Salamanca, Spain.
Sci Rep. 2020 Jul 24;10(1):12391. doi: 10.1038/s41598-020-68837-y.
Efficient sensory processing requires that the brain maximize its response to unexpected stimuli, while suppressing responsivity to expected events. Mismatch negativity (MMN) is an auditory event-related potential that occurs when a regular pattern is interrupted by an event that violates the expected properties of the pattern. According to the predictive coding framework there are two mechanisms underlying the MMN: repetition suppression and prediction error. MMN has been found to be reduced in individuals with schizophrenia, an effect believed to be underpinned by glutamate N-methyl-D-aspartate receptor (NMDA-R) dysfunction. In the current study, we aimed to test how the NMDA-R antagonist, MK-801 in the anaesthetized rat, affected repetition suppression and prediction error processes along the auditory thalamocortical pathway. We found that low-dose systemic administration of MK-801 differentially affect thalamocortical responses, namely, increasing thalamic repetition suppression and cortical prediction error. Results demonstrate an enhancement of neuronal mismatch, also confirmed by large scale-responses. Furthermore, MK-801 produces faster and stronger dynamics of adaptation along the thalamocortical hierarchy. Clearly more research is required to understand how NMDA-R antagonism and dosage affects processes contributing to MMN. Nonetheless, because a low dose of an NMDA-R antagonist increased neuronal mismatch, the outcome has implications for schizophrenia treatment.
有效的感觉处理要求大脑最大限度地对意外刺激做出反应，同时抑制对预期事件的反应。失匹配负波（MMN）是一种听觉事件相关电位，当一个规则模式被一个违反模式预期特性的事件打断时就会发生。根据预测编码框架，MMN 有两种机制：重复抑制和预测误差。研究发现，精神分裂症患者的 MMN 减少，这种效应被认为是由谷氨酸 N-甲基-D-天冬氨酸受体（NMDA-R）功能障碍引起的。在目前的研究中，我们旨在测试麻醉大鼠中 NMDA-R 拮抗剂 MK-801 如何影响听觉丘脑皮质通路中的重复抑制和预测误差过程。我们发现，低剂量系统给予 MK-801 会对丘脑皮质反应产生不同的影响，即增加丘脑重复抑制和皮质预测误差。结果表明神经元失匹配增强，大尺度反应也得到证实。此外，MK-801 还会沿丘脑皮质层次产生更快、更强的适应动力学。显然，需要进一步研究来理解 NMDA-R 拮抗作用和剂量如何影响 MMN 的产生过程。尽管如此，由于 NMDA-R 拮抗剂的低剂量增加了神经元失匹配，因此这一结果对精神分裂症的治疗具有重要意义。
