Reconfiguration of brain-wide neural activity after early life adversity.
Reconfiguration of brain-wide neural activity after early life adversity.
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早年逆境后全脑神经活动的重新配置。
DOI：
10.1101/2023.09.10.557058
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Bearer,ElaineL
中科院分区：
文献类型：
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作者：
Uselman,TaylorW;Jacobs,RussellE;Bearer,ElaineL
早期生活逆境（ELA）使个体终生容易出现身体和精神障碍。ELA如何影响大脑功能导致这种脆弱性正在进行深入调查。研究已经开始阐明ELA对定义回路内的局部大脑区域的影响。然而，对包括多个局部区域的全脑神经活动的调查，确定区域之间的活动关系，并识别响应于经验条件的活动变化是必要的。在这里，我们进行了纵向锰增强磁共振成像（MEMRI）成像正常饲养或ELA暴露的成年人的大脑。在自由移动的笼舍条件下以及自然主义威胁后的短期和长期捕获图像。用新的计算方法分析图像，包括自动分割和分数激活或差异体积。我们发现，与正常饲养相比，ELA后多个大脑区域的神经活动增加，其中一些涉及防御和/或奖励回路。广泛分布的神经活动模式，“大脑状态”，和他们的动态后，威胁与ELA改变。急性威胁后，ELA小鼠保留了许多这些地区的神经活动增强，新的过度活跃的反应出现在单胺能中心的中脑和后脑。9天后，急性威胁，提高神经活动仍然在蓝斑和增加后杏仁核，腹侧海马，背侧和腹内侧下丘脑，而减少活动出现在内侧前额叶皮质区域（前边缘，边缘下，前扣带）。这些结果表明，ELA后，依赖于上下文和累积经验的多个脑系统之间出现功能失衡。
Early life adversity (ELA) predisposes individuals to both physical and mental disorders lifelong. How ELA affects brain function leading to this vulnerability is under intense investigation. Research has begun to shed light on ELA effects on localized brain regions within defined circuits. However, investigations into brain-wide neural activity that includes multiple localized regions, determines relationships of activity between regions and identifies shifts of activity in response to experiential conditions is necessary. Here, we performed longitudinal manganese-enhanced magnetic resonance imaging (MEMRI) to image the brain in normally reared or ELA-exposed adults. Images were captured in the freely moving home cage condition, and short- and long-term after naturalistic threat. Images were analyzed with new computational methods, including automated segmentation and fractional activation or difference volumes. We found that neural activity was increased after ELA compared to normal rearing in multiple brain regions, some of which are involved in defensive and/or reward circuitry. Widely distributed patterns of neural activity, “brain states”, and their dynamics after threat were altered with ELA. Upon acute threat, ELA-mice retained heightened neural activity within many of these regions, and new hyperactive responses emerged in monoaminergic centers of the mid- and hindbrain. Nine days after acute threat, heightened neural activity remained within locus coeruleus and increased within posterior amygdala, ventral hippocampus, and dorso- and ventromedial hypothalamus, while reduced activity emerged within medial prefrontal cortical regions (prelimbic, infralimbic, anterior cingulate). These results reveal that functional imbalances arise between multiple brain-systems which are dependent upon context and cumulative experiences after ELA.