Psychology Department, University of Otago, Dunedin 9054, New Zealand.
J Neurosci. 2010 Sep 15;30(37):12424-31. doi: 10.1523/JNEUROSCI.3046-10.2010.
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.
神经放电的同步性被认为是大脑中神经网络之间和内部信息整合的基础。异常的远端脑区神经活动同步性被认为是精神分裂症核心症状的基础。本研究使用母体免疫激活（MIA）大鼠模型，研究了两个与精神分裂症病理生理学相关的脑区——内侧前额叶皮层（mPFC）和海马体（HPC）之间是否存在异常同步。这种精神分裂症的神经发育模型是通过在怀孕的母鼠中单次注射合成免疫系统激活剂聚肌胞苷酸（polyriboinosinic-polyribocytidylic acid）诱导的，聚肌胞苷酸是双链 RNA 的合成类似物，是与病毒感染相关的分子模式。它基于产前暴露于感染后成年期精神分裂症风险增加的流行病学证据。在本研究中，在自由活动的 MIA 和对照后代中测量了 EEG 相干性和神经元对基础 EEG 的相位锁定。MIA 干预导致 mPFC-HPC EEG 相干性显著降低，与惊吓前脉冲抑制（startle）降低相关，惊吓前脉冲抑制是一种感觉门控和精神分裂症行为特征的标志性测量。此外，在 theta 和低 gamma 频率下，神经元放电对基础 EEG 的同步性变化明显。在 MIA 动物中，theta 调制、gamma 同步的假定 mPFC 神经元群体内的放电也减少了。因此，MIA 在大鼠中产生了成年后代大脑中长程神经元同步性的根本破坏，该模型模拟了精神分裂症中观察到的同步性破坏。
