Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multi-modal stress
Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multi-modal stress
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DOI：
10.1038/mp.2014.64
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发表时间：
2014
影响因子：
11
通讯作者：
P. Maras;J. Molet;Y. Chen;C. Rice;S. G. Ji;A. Solodkin;T. Baram
中科院分区：
文献类型：
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作者：
P. Maras;J. Molet;Y. Chen;C. Rice;S. G. Ji;A. Solodkin;T. Baram
压力对认知的影响是深远的，但尚不清楚同时存在的多种压力对学习和记忆的影响是否与同等强度和持续时间的单一压力的影响不同。我们比较了同时存在的、持续数小时的光、大声的噪音、推挤和约束（多模式压力）与单独的约束或大声的噪音对海马依赖性记忆的影响。然后，我们检查了这两种压力类型后记忆障碍的差异是否可能源于它们对海马突触的不同影响，区分背侧和腹侧海马。暴露于长达数小时的约束或大声噪音的小鼠在新物体识别方面受到适度或轻微的损害，而持续时间相似的多模式应激会引发严重的缺陷。记忆力的差异不能用血浆皮质酮水平或应激敏感下丘脑神经元中 Fos 标记神经元数量的差异来解释。然而，尽管海马 CA3 中的突触受到约束和多模式压力的影响，但多模式压力本身会严重减少背侧 CA1 的突触数量，而背侧 CA1 是海马依赖性记忆的关键区域。腹侧 CA1 突触未受到任何一种应激方式的显着影响。探讨多模式应激后背侧突触优先丧失的基础，我们发现两种应激类型的神经元激活模式不同。互相关矩阵反映了激活区域之间的功能连接，表明多模式应激降低了海马与隔膜和丘脑的相关性，并增加了与杏仁核和 BST 的相关性。因此，尽管对血浆皮质酮和下丘脑应激敏感细胞的作用相似，但多模式应激和束缚应激在大脑网络的激活和对海马突触的影响方面有所不同。这两个过程都可能导致短暂的多模式压力后记忆损伤的加剧。
The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress.