记忆提取的遗传机制和神经环路研究

Memory retrieval is the process to access and re-activate the memories that have been encoded and stored. Memory retrieval plays an essential role in adapting the information obtained in the past to the changing environment, which is important for individual survival and population evolution. However, the molecular and cellular mechanisms of memory retrieval are still unraveled. Our preliminary work showed that the neurofibromatosis type 1 (NF1) gene not only bi-directionally regulated both aversive and reward long-term memory in Drosophila, but also was involved in the retrieval of long-term memory (LTM) instead of the acquisition and consolidation of LTM. In a preliminary screening, we found that NF1 regulated LTM in brain regions other than the mushroom body which is required in memory acquisition, and that octopaminergic neurons might play an important role in memory retrieval. We hope, with the support of this funding, to further explore the signaling pathways involved in the regulation of memory retrieval by NF1, to identify and refine the neural circuits involved in memory retrieval and to find the correlation between neuronal activity in these circuits and the behavioral output of memory retrieval. These endeavors would help us to understand the molecular mechanisms and neural circuits in memory retrieval.

记忆的提取是一个将过去存储在脑中的信息重新激活并加以应用的过程。作为生物体将过去获得的信息加以应用以适应环境的过程，记忆的提取对个体生存和种群进化有着十分重要的意义。然而，目前人们对记忆提取的分子细胞机制知之甚少。在本计划前期工作中，我们发现神经纤维瘤病1型（NF1）基因不仅可以双向调控果蝇的惩罚性和奖赏性的长时程记忆，而且是通过参与记忆提取过程来实现对长时记忆的调控的。在初步筛选中，我们发现与对记忆获取阶段的调控不同，NF1对长时记忆的调控是在蘑菇体以外的脑区进行的，而章鱼胺能神经元可能是参与NF1调控记忆提取的重要神经环路。我们希望通过这一项目深入探索参与NF1调控记忆提取过程的信号通路，细化参与记忆提取过程的神经环路，并探寻这些神经环路神经元的兴奋性与记忆提取行为的相关性，加深我们对记忆提取分子机制和神经环路的理解，培养6-8位研究生和1-2位博士后，发表2-3篇高质量的论文。

记忆的提取是将学习时形成的记忆痕迹细胞重新激活并用以指挥行为选择以便更好适应环境的过程。这个关键的过程对于生物个体和种群繁衍具有重要意义。记忆提取是一个复杂而精细的过程。记忆痕迹的形成，巩固和遗忘都会影响到记忆的提取。围绕着与记忆提取有关的遗传机制和神经环路，本项目从四个不同角度对记忆提取进行了系统的研究：参与记忆提取的分子机制与神经环路研究、遗忘对记忆提取的影响研究、记忆提取障碍相关疾病的研究、以及记忆形成与固化对于提取的影响研究。通过这四方面的研究，我们深入探索了调控记忆提取过程的信号通路，细化了参与记忆提取过程的神经环路，加深了我们对记忆提取分子机制和神经环路的理解，并且对相关疾病的研究与治疗提供了新的病理机制与治疗思路。