Abnormal Long-Range Neural Synchrony in a Maternal Immune Activation Animal Model of Schizophrenia
Abnormal Long-Range Neural Synchrony in a Maternal Immune Activation Animal Model of Schizophrenia
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DOI：
10.1523/jneurosci.3046-10.2010
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发表时间：
2010-09-15
影响因子：
5.3
通讯作者：
Bilkey, David K.
中科院分区：
文献类型：
--
作者：
Dickerson, Desiree D.;Wolff, Amy R.;Bilkey, David K.
神经放电的同步性被认为是大脑神经网络之间和内部信息整合的基础。精神分裂症的核心症状学基础是远端脑区神经活动的异常同步。本研究采用大鼠母体免疫激活(MIA)动物模型，研究了与精神分裂症病理生理学有关的两个脑区--内侧前额叶皮质(MPFC)和海马区(HPC)之间是否发生异常同步。这种精神分裂症的神经发育模型是通过在怀孕的大鼠水坝中单次注射合成免疫系统激活剂多核苷多核糖核酸诱导的，多聚核糖核糖核酸是双链RNA的合成类似物，双链RNA是一种与病毒感染相关的分子模式。它是基于流行病学证据，即在产前暴露于感染后，成年后患精神分裂症的风险增加。在本研究中，测量了自由活动的MIA和对照子代的脑电一致性和神经元对潜在脑电的相位锁定。MIA干预导致mPFC-HPC脑电一致性显著降低，这与惊吓的脉冲前抑制减少相关，脉冲前抑制是感官门控的一种衡量标准，也是分裂类型行为的一项标志性衡量标准。此外，神经元放电与潜在脑电同步的变化在theta和低伽马频率上也很明显。在MIA动物中，推测的theta调节的、伽马携带的mPFC神经元群体中的放电也减少了。因此，在大鼠中，MIA在成年后代的大脑中产生了长程神经元同步性的根本中断，这就是在精神分裂症中观察到的同步性中断的模型。
The synchrony of neural firing is believed to underlie the integration of information between and within neural networks in the brain. Abnormal synchronization of neural activity between distal brain regions has been proposed to underlie the core symptomatology in schizophrenia. This study investigated whether abnormal synchronization occurs between the medial prefrontal cortex (mPFC) and the hippocampus (HPC), two brain regions implicated in schizophrenia pathophysiology, using the maternal immune activation (MIA) animal model in rats. This neurodevelopmental model of schizophrenia is induced through a single injection of the synthetic immune system activator polyriboinosinic-polyribocytidylic acid, a synthetic analog of double-stranded RNA, a molecular pattern associated with viral infection, in pregnant rat dams. It is based on epidemiological evidence of increased risk of schizophrenia in adulthood after prenatal exposure to infection. In the present study, EEG coherence and neuronal phase-locking to underlying EEG were measured in freely moving MIA and control offspring. The MIA intervention produced significant reductions in mPFC-HPC EEG coherence that correlated with decreased prepulse inhibition of startle, a measure of sensory gating and a hallmark schizotypal behavioral measure. Furthermore, changes in the synchronization of neuronal firing to the underlying EEG were evident in the theta and low-gamma frequencies. Firing within a putative population of theta-modulated, gamma-entrained mPFC neurons was also reduced in MIA animals. Thus, MIA in rats produces a fundamental disruption in long-range neuronal synchrony in the brains of the adult offspring that models the disruption of synchrony observed in schizophrenia.