Environmental enrichment normalizes hippocampal timing coding in a malformed hippocampus.
Environmental enrichment normalizes hippocampal timing coding in a malformed hippocampus.
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DOI：
10.1371/journal.pone.0191488
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Scott RC
中科院分区：
文献类型：
--
作者：
Hernan AE;Mahoney JM;Curry W;Richard G;Lucas MM;Massey A;Holmes GL;Scott RC
神经发育损伤导致皮质发育畸形（MCD）是精神障碍、学习障碍和癫痫的常见原因。在mcd的甲基氧化甲醇（MAM）模型中，断奶后环境富集（EE）显著改善了动物的空间认知障碍。为了确定情感表达如何影响网络层面的空间认知机制，在一个开放的舞台上对自由运动的动物进行了海马体内单单位记录。我们采用广义线性建模方法提取精细脉冲时序（FST）特征，并将这些特征与位置细胞保真度联系起来，作为空间认知的替代指标。我们发现MAM破坏了海马CA1中的FST和位置调制速率编码，而EE使许多FST参数趋于正常。此外，FST参数预测神经元的空间一致性，表明决定FST改变的机制是mcd认知功能受损的原因。这表明，FST参数可以代表一个治疗靶点，即使在大脑结构异常的情况下，也可以改善认知。
Neurodevelopmental insults leading to malformations of cortical development (MCD) are a common cause of psychiatric disorders, learning impairments and epilepsy. In the methylazoxymethanol (MAM) model of MCDs, animals have impairments in spatial cognition that, remarkably, are improved by post-weaning environmental enrichment (EE). To establish how EE impacts network-level mechanisms of spatial cognition, hippocampal in vivo single unit recordings were performed in freely moving animals in an open arena. We took a generalized linear modeling approach to extract fine spike timing (FST) characteristics and related these to place cell fidelity used as a surrogate of spatial cognition. We find that MAM disrupts FST and place-modulated rate coding in hippocampal CA1 and that EE improves many FST parameters towards normal. Moreover, FST parameters predict spatial coherence of neurons, suggesting that mechanisms determining altered FST are responsible for impaired cognition in MCDs. This suggests that FST parameters could represent a therapeutic target to improve cognition even in the context of a brain that develops with a structural abnormality.
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