Department of Psychology, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Department of Psychology, Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Brain Behav Immun. 2015 Aug;48:232-43. doi: 10.1016/j.bbi.2015.03.012. Epub 2015 Apr 3.
Prenatal maternal immune activation (MIA) is a risk factor for several developmental neuropsychiatric disorders, including autism, bipolar disorder and schizophrenia. Adults with these disorders display alterations in memory function that may result from changes in the structure and function of the hippocampus. In the present study we use an animal model to investigate the effect that a transient prenatal maternal immune activation episode has on the spatially-modulated firing activity of hippocampal neurons in adult animals. MIA was induced in pregnant rat dams with a single injection of the synthetic cytokine inducer polyinosinic:polycytidylic acid (poly I:C) on gestational day 15. Control dams were given a saline equivalent. Firing activity and local field potentials (LFPs) were recorded from the CA1 region of the adult male offspring of these dams as they moved freely in an open arena. Most neurons displayed characteristic spatially-modulated 'place cell' firing activity and while there was no between-group difference in mean firing rate between groups, place cells had smaller place fields in MIA-exposed animals when compared to control-group cells. Cells recorded in MIA-group animals also displayed an altered firing-phase synchrony relationship to simultaneously recorded LFPs. When the floor of the arena was rotated, the place fields of MIA-group cells were more likely to shift in the same direction as the floor rotation, suggesting that local cues may have been more salient for these animals. In contrast, place fields in control group cells were more likely to shift firing position to novel spatial locations suggesting an altered response to contextual cues. These findings show that a single MIA intervention is sufficient to change several important characteristics of hippocampal place cell activity in adult offspring. These changes could contribute to the memory dysfunction that is associated with MIA, by altering the encoding of spatial context and by disrupting plasticity mechanisms that are dependent on spike timing synchrony.
产前母体免疫激活（MIA）是多种发育性神经精神疾病的风险因素，包括自闭症、双相情感障碍和精神分裂症。患有这些疾病的成年人表现出记忆功能的改变，这可能是由于海马结构和功能的变化所致。在本研究中，我们使用动物模型来研究短暂的产前母体免疫激活事件对成年动物海马神经元的空间调制放电活动的影响。在妊娠第 15 天，用合成细胞因子诱导剂聚肌苷酸：聚胞苷酸（poly I:C）对孕鼠进行单次注射诱导 MIA。对照鼠给予等渗盐水。在这些母鼠的雄性后代成年后，当它们在开放场中自由移动时，从 CA1 区域记录放电活动和局部场电位（LFPs）。大多数神经元表现出特征性的空间调制“位置细胞”放电活动，虽然两组之间的平均放电率没有组间差异，但与对照组细胞相比，MIA 暴露动物的位置细胞的位置场较小。在 MIA 组动物中记录的细胞也表现出与同时记录的 LFPs 的改变的放电相位同步关系。当竞技场的地板旋转时，MIA 组细胞的位置场更有可能与地板旋转的方向相同，这表明对于这些动物，局部线索可能更明显。相比之下，对照组细胞的位置场更有可能将放电位置转移到新的空间位置，这表明对上下文线索的反应发生了改变。这些发现表明，单次 MIA 干预足以改变成年后代海马位置细胞活动的几个重要特征。这些变化可能通过改变空间上下文的编码和破坏依赖于尖峰时间同步的可塑性机制，导致与 MIA 相关的记忆功能障碍。
