The Making of Long-Lasting Memories: A Fruit Fly Perspective.

The Making of Long-Lasting Memories: A Fruit Fly Perspective.
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DOI:
10.3389/fnbeh.2021.662129
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发表时间:
2021
影响因子:
3
通讯作者:
Cervantes-Sandoval I
Cervantes-Sandoval I
中科院分区:
医学3区
文献类型:
--
作者:
Roselli C;Ramaswami M;Boto T;Cervantes-Sandoval I

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了解记忆形成、巩固和遗忘背后的分子机制的本质是现代神经科学中一些令人着迷的问题。记忆的编码、稳定和消除,依赖于突触的结构重组。这些变化将使神经活动能够促进或抑制对新信息的获取。换句话说,这些变化会影响神经网络中特定节点的权重。我们知道,这些可塑性重组需要在长期记忆(LTM)的背景下从头合成蛋白质。这个过程依赖于学习到的经验所触发的神经活动。事实证明,像黑腹果蝇这样的模式生物的使用对于增进我们在神经科学领域的知识是必不可少的。苍蝇提供了一个更简单的神经系统的最佳组合,由有限数量的细胞组成,同时仍然表现出复杂的行为。经过几十年的发展,果蝇神经科学的研究对于理解在学习和记忆背景下发生的突触和行为可塑性的细胞和分子机制至关重要。这是可能的,这要归功于复杂的技术方法,这些方法能够精确控制果蝇的基因表达,以及神经操作,如化学遗传学、热遗传学或光遗传学。自从行为遗传学起源以来,寻找记忆获得所表达的基因的身份一直是一个活跃的兴趣。从筛选或多或少特定的候选者到基于转录组分析的更广泛的研究,我们对LTM背后的基因控制的理解在过去几年里呈指数级增长。在这里,我们回顾了最近的文献,关于记忆的形成如何诱导快速的,广泛的,在许多情况下,瞬时的转录活动波。经过一段时间的巩固后,转录组的变化似乎更稳定,可能代表了新蛋白质的合成。参与记忆形成和巩固的电路非常复杂,以至于神经活动在时间动力学和受影响的神经元和亚细胞位置的性质方面都有局限性的变化,从而导致蛋白质表达的特定的时间性和局部性变化。不同类型的神经元在不同的时间被招募到记忆痕迹中。在LTM中,在特定的细胞亚群中需要合成新的蛋白质。这种从头翻译可以发生在体细胞质和/或局部区划的突触活动区,这取决于蛋白质的性质和发生的可塑性诱导过程。我们还将回顾在理解局部变化如何局限于相关突触方面的最新进展。这些最近的研究导致了关于以前没有参与学习和记忆过程的蛋白质的令人兴奋的发现。这些宝贵的信息将导致未来对数百个新的分子参与者在调节神经活动中所扮演的角色的功能研究。
Understanding the nature of the molecular mechanisms underlying memory formation, consolidation, and forgetting are some of the fascinating questions in modern neuroscience. The encoding, stabilization and elimination of memories, rely on the structural reorganization of synapses. These changes will enable the facilitation or depression of neural activity in response to the acquisition of new information. In other words, these changes affect the weight of specific nodes within a neural network. We know that these plastic reorganizations require de novo protein synthesis in the context of Long-term memory (LTM). This process depends on neural activity triggered by the learned experience. The use of model organisms like Drosophila melanogaster has been proven essential for advancing our knowledge in the field of neuroscience. Flies offer an optimal combination of a more straightforward nervous system, composed of a limited number of cells, and while still displaying complex behaviors. Studies in Drosophila neuroscience, which expanded over several decades, have been critical for understanding the cellular and molecular mechanisms leading to the synaptic and behavioral plasticity occurring in the context of learning and memory. This is possible thanks to sophisticated technical approaches that enable precise control of gene expression in the fruit fly as well as neural manipulation, like chemogenetics, thermogenetics, or optogenetics. The search for the identity of genes expressed as a result of memory acquisition has been an active interest since the origins of behavioral genetics. From screenings of more or less specific candidates to broader studies based on transcriptome analysis, our understanding of the genetic control behind LTM has expanded exponentially in the past years. Here we review recent literature regarding how the formation of memories induces a rapid, extensive and, in many cases, transient wave of transcriptional activity. After a consolidation period, transcriptome changes seem more stable and likely represent the synthesis of new proteins. The complexity of the circuitry involved in memory formation and consolidation is such that there are localized changes in neural activity, both regarding temporal dynamics and the nature of neurons and subcellular locations affected, hence inducing specific temporal and localized changes in protein expression. Different types of neurons are recruited at different times into memory traces. In LTM, the synthesis of new proteins is required in specific subsets of cells. This de novo translation can take place in the somatic cytoplasm and/or locally in distinct zones of compartmentalized synaptic activity, depending on the nature of the proteins and the plasticity-inducing processes that occur. We will also review recent advances in understanding how localized changes are confined to the relevant synapse. These recent studies have led to exciting discoveries regarding proteins that were not previously involved in learning and memory processes. This invaluable information will lead to future functional studies on the roles that hundreds of new molecular actors play in modulating neural activity.
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