James H. Clark Center for Biomedical Engineering & Sciences, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; CNC Program, Stanford University, Stanford, CA 94305, USA; Department of Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, 80804 Munich, Germany.
James H. Clark Center for Biomedical Engineering & Sciences, Stanford University, Stanford, CA 94305, USA.
Cell Rep. 2018 Oct 16;25(3):640-650.e2. doi: 10.1016/j.celrep.2018.09.064.
Neural network remodeling underpins the ability to remember life experiences, but little is known about the long-term plasticity of neural populations. To study how the brain encodes episodic events, we used time-lapse two-photon microscopy and a fluorescent reporter of neural plasticity based on an enhanced form of the synaptic activity-responsive element (E-SARE) within the Arc promoter to track thousands of CA1 hippocampal pyramidal cells over weeks in mice that repeatedly encountered different environments. Each environment evokes characteristic patterns of ensemble neural plasticity, but with each encounter, the set of activated cells gradually evolves. After repeated exposures, the plasticity patterns evoked by an individual environment progressively stabilize. Compared with young adults, plasticity patterns in aged mice are less specific to individual environments and less stable across repeat experiences. Long-term consolidation of hippocampal plasticity patterns may support long-term memory formation, whereas weaker consolidation in aged subjects might reflect declining memory function.
神经网络重塑是记忆生活经历的基础，但人们对神经群体的长期可塑性知之甚少。为了研究大脑如何对情景事件进行编码，我们使用延时双光子显微镜和一种基于 Arc 启动子中增强型突触活动反应元件 (E-SARE) 的神经可塑性荧光报告基因，在反复遇到不同环境的小鼠中跟踪 CA1 海马锥体细胞数千个，持续数周。每个环境都会引发特征性的整体神经可塑性模式，但每次接触，激活细胞的集合都会逐渐演变。经过多次暴露，单个环境引发的可塑性模式会逐渐稳定下来。与年轻成年人相比，老年小鼠的可塑性模式对单个环境的特异性较差，在重复体验中也不太稳定。海马体可塑性模式的长期巩固可能支持长期记忆的形成，而老年受试者的巩固较弱可能反映出记忆功能的下降。
