NMDA receptor hypofunction leads to generalized and persistent aberrant gamma oscillations independent of hyperlocomotion and the state of consciousness.
NMDA receptor hypofunction leads to generalized and persistent aberrant gamma oscillations independent of hyperlocomotion and the state of consciousness.
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DOI：
10.1371/journal.pone.0006755
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发表时间：
2009-08-25
期刊：
影响因子：
3.7
通讯作者：
Pinault D
中科院分区：
文献类型：
--
作者：
Hakami T;Jones NC;Tolmacheva EA;Gaudias J;Chaumont J;Salzberg M;O'Brien TJ;Pinault D
拟精神病药氯胺酮和MK-801是非竞争性NMDA受体（NMDAr）拮抗剂，可诱导认知障碍并加剧精神分裂症症状。在清醒大鼠中，它们产生与特殊脑状态相关的异常行为，其特征在于额顶（感觉运动）皮层电图（ECoG）中持续γ（30-80 Hz）振荡的同步性增加。本研究探讨了NMDAr拮抗剂诱导的异常γ振荡是否与运动相关，并依赖于超运动相关的感觉运动加工。这也意味着探索皮层内和皮层下网络在这些病理生理ECoG γ振荡产生中的作用。使用计算机辅助视频跟踪系统结合ECoG收集的定量运动数据显示，氯胺酮和MK-801诱导高度相关的过度运动和异常γ振荡。额叶、顶叶和枕叶皮质都记录到这种异常的γ活动过度。在不同意识状态（使用不同麻醉剂）下进行的ECoG显示，NMDAr拮抗剂显著增加基础γ振荡的功率。皮层电图和皮层内局部场电位的配对记录表明，皮层电图主要反映了皮层内网络的γ振荡。此外，多位点记录显示，NMDAr拮抗剂可显着增强多个皮质和皮质下结构（包括前额叶皮质、伏隔核、杏仁核、基底核、海马体、纹状体和丘脑）中正在进行的γ振荡量。NMDAr拮抗剂在啮齿动物CNS中急性产生全身异常γ振荡，其不依赖于过度运动相关的脑状态或有意识感觉运动处理。这些发现表明，NMDAr功能减退相关的广义γ超同步性代表了一种异常的弥漫性网络噪声，这是一种潜在的精神病样状态的电生理相关性。这种普遍的噪音可能会导致大脑运作功能障碍，包括精神分裂症中的认知和感觉运动整合障碍。
The psychotomimetics ketamine and MK-801, non-competitive NMDA receptor (NMDAr) antagonists, induce cognitive impairment and aggravate schizophrenia symptoms. In conscious rats, they produce an abnormal behavior associated with a peculiar brain state characterized by increased synchronization in ongoing γ (30–80 Hz) oscillations in the frontoparietal (sensorimotor) electrocorticogram (ECoG). This study investigated whether NMDAr antagonists-induced aberrant γ oscillations are correlated with locomotion and dependent on hyperlocomotion-related sensorimotor processing. This also implied to explore the contribution of intracortical and subcortical networks in the generation of these pathophysiological ECoG γ oscillations. Quantitative locomotion data collected with a computer-assisted video tracking system in combination with ECoG revealed that ketamine and MK-801 induce highly correlated hyperlocomotion and aberrant γ oscillations. This abnormal γ hyperactivity was recorded over the frontal, parietal and occipital cortices. ECoG conducted under diverse consciousness states (with diverse anesthetics) revealed that NMDAr antagonists dramatically increase the power of basal γ oscillations. Paired ECoG and intracortical local field potential recordings showed that the ECoG mainly reflects γ oscillations recorded in underlying intracortical networks. In addition, multisite recordings revealed that NMDAr antagonists dramatically enhance the amount of ongoing γ oscillations in multiple cortical and subcortical structures, including the prefrontal cortex, accumbens, amygdala, basalis, hippocampus, striatum and thalamus. NMDAr antagonists acutely produces, in the rodent CNS, generalized aberrant γ oscillations, which are not dependent on hyperlocomotion-related brain state or conscious sensorimotor processing. These findings suggest that NMDAr hypofunction-related generalized γ hypersynchronies represent an aberrant diffuse network noise, a potential electrophysiological correlate of a psychotic-like state. Such generalized noise might cause dysfunction of brain operations, including the impairments in cognition and sensorimotor integration seen in schizophrenia.
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