Early Alterations in Hippocampal Circuitry and Theta Rhythm Generation in a Mouse Model of Prenatal Infection: Implications for Schizophrenia
Early Alterations in Hippocampal Circuitry and Theta Rhythm Generation in a Mouse Model of Prenatal Infection: Implications for Schizophrenia
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DOI：
10.1371/journal.pone.0029754
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发表时间：
2012-01-06
期刊：
影响因子：
3.7
通讯作者：
Williams, Sylvain
中科院分区：
文献类型：
--
作者：
Ducharme, Guillaume;Lowe, Germaine C.;Williams, Sylvain
尸检研究表明，精神分裂症患者的GABA能神经传递功能受损。然而，目前尚不清楚这些变化是否发生在开发的早期阶段，以及它们如何影响整体网络活动。为了研究这一点，我们使用了一种带有病毒模拟物聚核苷多聚核糖核酸(PolyI：C)的产前感染小鼠模型，该模型基于流行病学证据，即怀孕期间的免疫挑战会增加后代精神分裂症的患病率。我们发现，产前感染降低了海马区CA1区小白蛋白阳性中间神经元的密度，但不减少生长抑素阳性中间神经元的密度，并在出生后发育早期强烈降低了抑制强度。此外，使用完整的体外海马体标本，我们发现CA1区产生的theta振荡减少。综上所述，这些结果表明，CA1局部兴奋性和抑制性传递的重新分布与网络功能的显著变化有关。此外，考虑到theta节奏在记忆中的作用，我们的结果表明，精神分裂症的风险因素如何影响发育早期的网络功能，这可能导致后来在疾病中观察到的认知缺陷。
Post-mortem studies suggest that GABAergic neurotransmission is impaired in schizophrenia. However, it remains unclear if these changes occur early during development and how they impact overall network activity. To investigate this, we used a mouse model of prenatal infection with the viral mimic, polyriboinosinic-polyribocytidilic acid (poly I: C), a model based on epidemiological evidence that an immune challenge during pregnancy increases the prevalence of schizophrenia in the offspring. We found that prenatal infection reduced the density of parvalbumin-but not somatostatin-positive interneurons in the CA1 area of the hippocampus and strongly reduced the strength of inhibition early during postnatal development. Furthermore, using an intact hippocampal preparation in vitro, we found reduced theta oscillation generated in the CA1 area. Taken together, these results suggest that redistribution in excitatory and inhibitory transmission locally in the CA1 is associated with a significant alteration in network function. Furthermore, given the role of theta rhythm in memory, our results demonstrate how a risk factor for schizophrenia can affect network function early in development that could contribute to cognitive deficits observed later in the disease.