Kyrke-Smith Madeleine, Williams Joanna M
Department of Anatomy, The Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
Department of Psychology, The Brain Health Research Centre, Brain Research New Zealand - Rangahau Roro Aotearoa, University of Otago, Dunedin, New Zealand.
Front Mol Neurosci. 2018 Oct 5;11:369. doi: 10.3389/fnmol.2018.00369. eCollection 2018.
How memories are maintained, and how memories are lost during aging or disease, are intensely investigated issues. Arguably, the reigning theory is that synaptic modifications allow for the formation of engrams during learning, and sustaining engrams sustains memory. Activity-regulated gene expression profiles have been shown to be critical to these processes, and their control by the epigenome has begun to be investigated in earnest. Here, we propose a novel theory as to how engrams are sustained. We propose that many of the genes that are currently believed to underlie long-term memory are actually part of a "plasticity transcriptome" that underpins structural and functional modifications to neuronal connectivity during the hours to days following learning. Further, we hypothesize that a "maintenance transcriptome" is subsequently induced that includes epigenetic negative regulators of gene expression, particularly histone deacetylases. The maintenance transcriptome negatively regulates the plasticity transcriptome, and thus the plastic capability of a neuron, after learning. In this way, the maintenance transcriptome would act as a metaplasticity mechanism that raises the threshold for change in neurons within an engram, helping to ensure the connectivity is stabilized and memory is maintained.
记忆是如何维持的，以及记忆在衰老或疾病过程中是如何丧失的，是深入研究的问题。可以说，目前占主导地位的理论是，突触修饰允许在学习过程中形成记忆痕迹，而维持记忆痕迹则维持记忆。活动调节的基因表达谱已被证明对这些过程至关重要，并且表观基因组对其的控制已开始得到认真研究。在这里，我们提出了一种关于记忆痕迹如何维持的新理论。我们提出，目前被认为是长期记忆基础的许多基因实际上是“可塑性转录组”的一部分，该转录组在学习后的数小时至数天内支持神经元连接的结构和功能修饰。此外，我们假设随后会诱导一个“维持转录组”，其中包括基因表达的表观遗传负调节因子，特别是组蛋白脱乙酰酶。维持转录组在学习后对可塑性转录组进行负调节，从而对神经元的可塑性能力进行负调节。通过这种方式，维持转录组将作为一种元可塑性机制，提高记忆痕迹内神经元变化的阈值，有助于确保连接稳定并维持记忆。
