New myelin for old memories.
New myelin for old memories.
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旧记忆的新髓磷脂。
DOI：
10.1038/s41386-021-01106-2
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Kheirbek,MazenA
中科院分区：
文献类型：
--
作者：
Kern,MichaelC;Kheirbek,MazenA
制造和存储记忆需要在可塑性和稳定性之间取得微妙的平衡，将灵活的信息编码和高保真存储相结合，以实现准确的回忆。新的记忆如何被整合到现有的网络中，以及这些网络是否/如何在很长一段时间内保持稳定，仍然是一个活跃的研究领域。越来越多的证据表明，依赖经验的髓鞘形成是成人大脑可塑性的一种重要形式。在啮齿动物中，少突胶质细胞在社交隔离后减少[1]，在运动[2]或空间学习后增加[3]。我们最近的工作表明，情景恐惧学习可以迅速诱导内侧前额叶皮质少突胶质前体细胞(OPC)增殖和分化为髓鞘少突胶质细胞(OLs)[4]。缺乏产生新髓鞘能力的小鼠，会损害对遥远但不是最近形成的恐惧记忆的回忆。此外，增加新髓鞘形成的药物干预增强了正常小鼠的远程恐惧记忆[4]。这些研究提出了一种有趣的可能性，即依赖经验的髓鞘形成促进了跨大脑区域的整体耦合，以支持协调恐惧记忆网络的生成。在恐惧学习之后，OPC在mPFC中增殖并成熟为有髓鞘的OL[4]，而操纵髓鞘形成改变了整个海马-前额叶-杏仁核网络中神经丛的活动和协调[3，4]。关于这一过程的基本机制问题仍然存在。例如，虽然恐惧学习诱导的少突胶质细胞形成很快，但紧密的髓鞘需要数周时间才能形成[4]。依赖经验的OL产生如何在这些不同的时间尺度上调节电路功能以支持不同阶段的记忆是未来研究的重要领域。此外，识别在恐惧学习后变得有髓鞘的皮质轴突，并确定选择轴突进行髓鞘形成的活动依赖和/或分子机制，可以为恐惧记忆是如何巩固的提供重要的见解。开发用于局部或特定细胞类型的新髓鞘形成操作的工具将使更有针对性的实验成为可能。将其与高密度、全脑记录技术[5]相结合，将提供前所未有的洞察力，了解依赖经验的髓鞘形成如何为时间上精确的信息流组织记忆集合。虽然有些记忆会在几天内消失，但许多记忆不会消失，特别是创伤记忆，几年后可以高精度地回忆起来。这一新兴领域确定了一种基于神经胶质的机制，用于系统水平巩固恐惧记忆，从而为治疗与记忆相关的焦虑症提供了一个新的潜在靶点，如创伤后应激
Making and storing memories requires an exquisite balance of plasticity and stability, combining flexible information coding and high-fidelity storage for accurate recall. How new memories are incorporated into existing networks and if/how these networks remain stable over long periods of time remains an active area of investigation.Emerging evidence suggests that experience-dependent myelination is an important form of plasticity in the adult brain. In rodents, oligodendrogenesis is reduced after social isolation [1] and increased after motor [2] or spatial learning [3]. Our recent work indicates that context fear learning can rapidly induce oligodendrocyte precursor cell (OPC) proliferation and differentiation into myelinating oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC)[4]. Mice lacking the ability to generate new myelin have impaired recall of remote but not recently formed fear memories. In addition, pharmacological interventions that increase new myelin formation strengthen remote fear memory recall in normal mice [4]. These studies raise the intriguing possibility that experiencedependent myelination promotes the coupling of ensembles across brain regions to support the generation of a coordinated fear memory network. After fear learning, OPCs proliferate and mature into myelinating OLs in the mPFC [4], and manipulating myelin formation alters activity and coordination in neural ensembles across the entire hippocampal-prefrontal-amygdala network [3, 4]. Fundamental mechanistic questions about this process remain. For example, while fear learning-induced oligodendrogenesis is rapid, compact myelin takes weeks to form [4]. How experience-dependent OL production may modulate circuit function across these different time scales to support distinct stages of memory is an important area of future investigation. In addition, identifying the cortical axons that become myelinated after fear learning and determining the activitydependent and/or molecular mechanisms that select axons for myelination can shed important insight into how fear memories are consolidated. Development of tools for regional or cell type-specific manipulations of new myelin formation will enable more targeted experiments. Pairing this with high density, brain-wide recording techniques [5] will provide unprecedented insight into how experience-dependent myelination may serve to organize memory ensembles for temporally precise information flow. While some memories fade away in a few days, many do not, especially in the case of traumatic memories, which can be recalled with high precision years later. This emerging field identifies a glialbased mechanism for the systems-level consolidation of a fear memory and thus presents a novel potential target for the treatment of memory-related anxiety disorders, such as post-traumatic stress