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大鼠失匹配负波机制及其在大鼠精神分裂症模型中的应用
Alternative TitleThe mechanism of MMN (mismatch negativity) and its feasibility using as an index in the schizophreni
刘瀛瀛
Subtype博士
Thesis Advisor罗非
2012-05
Degree Grantor中国科学院研究生院
Place of Conferral北京
Degree Discipline心理学
KeywordMmn 清醒 麻醉 Isi 精神分裂症模型
Abstract摘要 失匹配负波(mismatch negativity,MMN)指由oddball范式中偏差刺激与标准刺激间的可辨差异所诱发的脑电成分。MMN代表了认知系统对刺激差别的自动探测,并且这种前注意的探测基本不需要占用注意资源,受意识状态的影响也相当有限。在精神分裂症患者上能够观察到显著的MMN减弱,该现象反应了精神分裂症患者认知加工能力受损,MMN被认为可能成为指示精神分裂症的神经生理指标。相对于人类MMN研究,动物MMN研究目前并没有得到统一的结论,并且在清醒动物上的研究甚少。本研究利用大鼠多电极脑电技术,探索大鼠MMN反应的机制,并且探索了清醒大鼠MMN是否有效指示了精神分裂症模型的建立。主要结果如下: 1、清醒大鼠与麻醉大鼠的MMN反应模式不同。在相同实验条件下,通过oddball范式,在清醒大鼠上得到了负向差异波,而在麻醉大鼠上得到正向差异波。 2、相对于1000ms与2000ms刺激间隔(inter-stimulus interbal,ISI),在3000ms ISI下能够得到波幅更高的MMN反应。 3、NMDA受体拮抗剂MK-801显著削弱了大鼠MMN反应。 4、在建立精神分裂症模型后,清醒大鼠MMN反应波幅显著低于前测且显著低于控制组。 根据上述结果,我们得出如下结论: 首次同时在清醒大鼠与麻醉大鼠上诱发了MMN反应。对比二者可以看到,清醒大鼠的MMN反应表现为负向差异波,麻醉大鼠的MMN反应表现为正向差异波。进而验证前人研究中大鼠MMN反应朝向相反,是由于意识状态的转变对大鼠刺激差异加工的电生理信号有重要影响。 首次发现麻醉状态导致大鼠听觉诱发电位晚成分发生改变。清醒大鼠晚成分为慢波NSW,而麻醉大鼠晚成分为慢波P3。 首次发现在1000-3000 ms ISI范围内,下大鼠MMN幅度随ISI的延长而增高的现象。 首次将清醒大鼠MMN应用于精神分裂症模型研究,在公认的精神分裂症慢性动物模型上验证了,精神分裂症模型的建立导致大鼠MMN反应的降低。
Other Abstract 
Abstract Mismatch negativity (MMN) is the ERP component which is evoked by the obvious difference between the deviant stimuli and standard stimuli in the oddball paradigm. The MMN represents the automatic cognitive detection to the difference between distinct stimuli, this pre-attentive process needs little attention resource, and almost not affected by the consciousness states either. The MMN attenuation is generally found in schizophrenia patients, reflecting their cognition decline. The MMN is considered to be a potential neurophysiological index of schizophrenia. Comparing to MMN studies in human, the characterization of animal MMN is not conclusive so far, especially fewer studies support the awake animal MMN. This study uses the multi-channel EEG technique on rats, explores the mechanism of MMN in rats, and whether can it be used as an index to the shizhophrenia animal model as feasible as in schizophrenia patients. We have got results as below: 1、The MMN were different in awake and anesthetized rats. In the same experimental condition, we got negative difference wave in awake rat, but positive difference wave in anesthtized rat. 2、In 3000 ms inter-srimulus interval (ISI) condition, the rat’s MMN amplitude was significantly larger than 1000 ms and 2000 ms ISI conditions in both awake and anesthetize rats. 3、NMDA receptor antagonist MK-801 could significantly impaired the MMN in both awake and anesthetized rats. 4、The establishment of the PCP schizophrenia model made the MMN in awake rats significantly attenuated. In brief, we first compared the difference between MMN in awake rats and anesthetized rats, their featueres were described as follow: the same oddball paradigm evoked negative difference wave in awake rats and positive difference wave in anesthetized rats, they represented the same processing; meanwhile, unlike the human MMN, MMN in rats had several components rather than one; the MMN in rats would have larger amplitude in longer ISI condition between 1000 ms-3000 ms ISI condition; the consciousness states change would also effect the auditory ERP of rats. In addition, we demonstrated that the MMN in awake rat was a feasible index to the schizophrenia model of rats. 
Subject Area认知神经科学
Language中文
Document Type学位论文
Identifierhttp://ir.psych.ac.cn/handle/311026/20308
Collection健康与遗传心理学研究室
Affiliation中国科学院心理研究所
Recommended Citation
GB/T 7714
刘瀛瀛. 大鼠失匹配负波机制及其在大鼠精神分裂症模型中的应用[D]. 北京. 中国科学院研究生院,2012.
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