Transcriptomic Mechanisms of Formation and Persistence of Synapse Specific Long-Term Memory

突触特异性长期记忆形成和持续的转录组机制

• 批准号: 10609651
• 负责人: Sathyanarayanan V Puthanveettil
• 金额: $ 23.18万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-12 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10609651
• 关键词: Transcriptomic; Mechanisms; Formation; Persistence; Synapse

PROJECT SUMMARY Long-term memory (LTM) storage requires remodeling of pre-existing synapses and formation of new ones. While the necessity of transcription in the temporal phases of LTM such as formation and persistence has been described, we lack comprehensive information on how gene expression changes in a neural circuitry mediate the formation and persistence of LTM. In any of the animal models of learning, we do not know what components of the transcriptomes are recruited specifically in pre- or post-synaptic neurons for mediating the formation and persistence of LTM. Particularly we know very little about the gene expression changes required for the persistence of LTM. Lack of this knowledge is a critical barrier for deciphering the molecular underpinnings of synapse specificity and LTM. The central hypothesis of this proposal is that coordinated regulation of the pre- and the post-synaptic neuronal transcriptome mediate the formation and persistence of synapse specific LTM. We propose to test this hypothesis using the well-characterized neural circuitry of gill-withdrawal reflex (GWR) of the marine snail, Aplysia californica. Specifically, using a modified bifurcated sensory neuron-motor neuron culture, we will assess the changes in the subcellular transcriptome of pre-synaptic sensory neurons and post-synaptic motor neurons during the formation and persistence of the synapse specific LTM. Furthermore, the role of molecular motor kinesin mediated transport of RNAs from the cell body to synapses in synapse specific LTM will be determined. We anticipate that these experiments will facilitate the decoding of the gene expression program for the formation and persistence of LTM in components of a defined neural circuitry. Furthermore, our studies are expected to produce a ground- breaking impact on the basic biology of synapse specific LTM as well as to facilitate identification of novel candidates for the development of therapeutics for memory disorders.

项目概要 长期记忆（LTM）存储需要重塑预先存在的突触并形成新的突触 那些。而 LTM 的时间阶段（例如形成和持续）转录的必要性 已经描述过，我们缺乏关于神经回路中基因表达如何变化的全面信息 介导 LTM 的形成和持续。在任何学习动物模型中，我们不知道什么 转录组的成分被特异性地招募到突触前或突触后神经元中，以介导 LTM 的形成和持续。特别是我们对基因表达变化知之甚少 LTM 持续存在所必需的。缺乏这方面的知识是破译分子生物学的一个关键障碍。 突触特异性和 LTM 的基础。该提案的中心假设是协调 突触前和突触后神经元转录组的调节介导神经元的形成和 突触特异性 LTM 的持续性。我们建议使用特征良好的模型来检验这一假设 海蜗牛海兔的缩鳃反射（GWR）的神经回路。具体来说，使用 改良的分叉感觉神经元-运动神经元培养物，我们将评估亚细胞的变化 突触前感觉神经元和突触后运动神经元在形成和形成过程中的转录组 突触特异性 LTM 的持久性。此外，分子运动驱动蛋白介导的运输的作用 将确定突触特异性 LTM 中从细胞体到突触的 RNA 的数量。我们预计这些 实验将有助于解码基因表达程序的形成和持久性 定义的神经回路组件中的 LTM。此外，我们的研究预计将产生一个基础 对突触特异性 LTM 的基础生物学产生突破性影响，并促进新型突触 LTM 的识别 开发记忆障碍疗法的候选者。