The Electrophysiological Signature of Motivational Salience in Mice and Implications for Schizophrenia
The Electrophysiological Signature of Motivational Salience in Mice and Implications for Schizophrenia
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小鼠动机显着性的电生理特征及其对精神分裂症的影响
DOI：
10.1038/npp.2012.156
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发表时间：
2012
影响因子：
7.6
通讯作者：
Siegel
中科院分区：
文献类型：
--
作者：
Moessnang;Schneider;Siegel
根据异常显着性假说，精神分裂症患者的动机显着性归因受到严重破坏。为了提供研究潜在机制的转化方法，在正常小鼠和 MK-801 精神分裂症模型中检查了显着性归因的神经相关性。使用听觉奇怪范式评估内侧前额叶皮层（mPFC）对标准和异常音调的电生理反应。动机显着性是由对异常语气的厌恶性调节引起的。听觉诱发电位（AEP）分析显示，动机显着性对晚期额叶负性（LFN）有选择性调节，这种调节在整个 4 周的延迟期间持续存在。 MK-801 是一种 N-甲基-D-天冬氨酸受体拮抗剂，消除了条件反射小鼠对动机显着性的这种差异反应。相反，在非条件反射小鼠中观察到对异常音调的明显 LFN 反应，即感知上的显着音调。额叶晚期慢波选择性调节的发现表明，自上而下的处理和对动机显着刺激的情绪评估有所增加。特别是，LFN 被讨论为小鼠对消极之前的人类刺激的模拟，这反映了预期奖励或惩罚的准备过程。 MK-801 导致条件反射和非条件反射小鼠的正常反应中断，包括非条件反射小鼠的 LFN 异常增加。这种“假阴性”和“假阳性”反应模式表明显着性归因的退化，这表明 mPFC 反应与精神分裂症认知改变的转化研究相关。
According to the aberrant-salience hypothesis, attribution of motivational salience is severely disrupted in patients with schizophrenia. To provide a translational approach for investigating underlying mechanisms, neural correlates of salience attribution were examined in normal mice and in a MK-801 model of schizophrenia. Electrophysiological responses to standard and deviant tones were assessed in the medial prefrontal cortex (mPFC) using an auditory oddball paradigm. Motivational salience was induced by aversive conditioning to the deviant tone. Analysis of the auditory evoked potential (AEP) showed selective modulation of the late frontal negativity (LFN) by motivational salience, which persisted throughout a 4-week delay. MK-801, an N-methyl-D-aspartic acid receptor antagonist, abolished this differential response to motivational salience in conditioned mice. In contrast, a pronounced LFN response was observed towards the deviant, ie, perceptually salient tone, in nonconditioned mice. The finding of a selective modulation of a late frontal slow wave suggests increased top–down processing and emotional evaluation of motivationally salient stimuli. In particular, the LFN is discussed as the mouse analog to the human stimulus preceding negativity, which reflects preparatory processes in anticipation of reward or punishment. MK-801 led to a disruption of the normal response in conditioned and nonconditioned mice, including an aberrantly increased LFN in nonconditioned mice. This pattern of ‘false-negative’and ‘false-positive’responses suggests a degradation of salience attribution, which points to mPFC responses to be relevant for translational research on cognitive alterations in schizophrenia.
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影响因子：
22.4
作者：
LUBOW, RE
通讯作者：
LUBOW, RE
影响因子：
7.2
作者：
BOUTON, ME
通讯作者：
BOUTON, ME
影响因子：
11.3
作者：
Turetsky BI;Bilker WB;Siegel SJ;Kohler CG;Gur RE
通讯作者：
Gur RE
影响因子：
4.6
作者：
Horan, William P.;Wynn, Jonathan K.;Kring, Ann M.;Simons, Robert F.;Green, Michael F.
通讯作者：
Green, Michael F.
影响因子：
1.7
作者：
GULDIN, WO;PRITZEL, M;MARKOWITSCH, HJ
通讯作者：
MARKOWITSCH, HJ