Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress.
Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress.
复制标题
DOI：
10.1111/gbb.12840
复制
发表时间：
2023-04
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
应激与情境记忆缺陷有关，情境记忆缺陷可能介导创伤后应激障碍患者对创伤相关情境的回避。这些缺陷可能源于模式分离受损，即海马背侧齿状回-海马角3 （DG - CA3）回路对相似经历的独立表征，该回路允许对特定环境刺激做出适当的行为反应。DG中的神经发生受线粒体活性氧（ROS）产生的控制，并可能有助于模式分离。在实验1中，我们对应激后16天的大鼠进行了RNA测序，这些大鼠要么对与捕食者尿液相关的环境（回避者）产生条件性场所回避，要么没有（非回避者）。加权基因组相关网络分析显示，氧化磷酸化相关基因转录本的表达增加和轴突引导和胰岛素信号传导基因转录本的表达减少与回避行为有关。基于这些数据，在实验2中，我们假设与非回避者相比，回避者会表现出更高的海马（HPC） ROS生成和降低的对象模式分离（OPS）。与非应激对照组相比，应激损害了非回避组和回避组大鼠的模式分离性能，但令人惊讶的是，与非回避组相比，回避组表现出部分保留的模式分离性能和显著降低的ROS生成。应激大鼠较低的ROS生成与较好的OPS表现相关，但对照组的ROS生成与OPS表现无关。这些结果表明应激后HPC ROS生成与模式分离之间存在强烈的负相关，应激对这些结果变量的影响可能与避免应激配对环境有关。在分子、功能和行为水平上对捕食者气味应激的不同适应反应。情境回避与代谢、线粒体和合成代谢转录适应有关，并部分保留了海马背侧的模式分离。非回避者表现出ROS升高和海马背侧模式分离的完全丧失。应激（回避+非回避）大鼠的ROS生成与模式分离表现相关，但与对照组无关。
Stress is associated with contextual memory deficits, which may mediate avoidance of trauma‐associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus‐Cornu Ammonis 3 (DG‐CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine‐associated context (Avoiders), or do not (Non‐Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation‐associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signaling were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Nonavoiders. Stress impaired pattern separation performance in Non‐Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non‐Avoiders. Lower ROS production was associated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong negative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress‐paired context. Divergent adaptive responses to predator odor stress at the molecular, functional, and behavioral levels. Contextual avoidance is associated with metabolic, mitochondrial and anabolic transcriptional adaptations, and partly preserved pattern separation in the dorsal hippocampus. Non‐Avoiders show elevated ROS and total loss of dorsal hippocampal pattern separation. ROS production correlates with pattern separation performance in Stressed (Avoider + Non‐Avoider), but not Control rats.
登录
查看更多内容
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
9.3
作者：
Dohi K;Ohtaki H;Nakamachi T;Yofu S;Satoh K;Miyamoto K;Song D;Tsunawaki S;Shioda S;Aruga T
通讯作者：
Aruga T
影响因子：
7.4
作者：
Gill, Roop;Tsung, Allan;Billiar, Timothy
通讯作者：
Billiar, Timothy
影响因子：
11
作者：
Gray JD;Rubin TG;Hunter RG;McEwen BS
通讯作者：
McEwen BS
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y