Impact of myelin dynamics on functional network stability and memory persistence

髓磷脂动力学对功能网络稳定性和记忆持久性的影响

• 批准号: RGPIN-2018-05967
• 负责人: Wheeler, Anne
• 金额: $ 2.77万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=763307
• 关键词: Impact; myelin; dynamics; functional; network

A healthy brain will allow important memories to last for a long time and most everyday experiences to be forgotten. The establishment of brain-wide networks of coordinated nerve cell activation accompanies learning, and these networks are stabilized to support persistent memory and destabilized to cause forgetting. Plasticity the brain's ability to change is essential for network formation, stabilization and destabilization. The focus of most research has been on plasticity at the level of the connection points between nerve cells, where existing connections can be strengthened or weakened, as well as added or eliminated to form new networks or remodel existing ones. Axons are the long thin projections of nerve cells that conduct electrical impulses and allow for the integration of information between brain regions within networks. Precise timing of this information is crucial for network stability. Myelin, a component of support cells in the brain, insulates axons, thus the degree of myelination will affect the timing of electrical impulses. Myelination begins in the womb and progresses through childhood and adolescence and recent research has demonstrated that myelin keeps changing in adulthood. This brings to light another element of enduring plasticity changes in myelin whose influence on network stability and memory persistence is not known.The proposed research will focus on the influence of changes in myelin myelination during development and remodeling of myelin in adulthood on memory persistence and the stability of fear memory networks with the following short-term objectives: 1. To characterize the role of brain-wide myelin changes in fear memory persistence. 2. To model the effect of brain-wide myelin changes on fear memory network stability in a computer simulation. If the short-term objectives described here provide support for a specific role for myelin plasticity in memory persistence via network stability, many of the approaches can be translated to studies in humans in our lab. This is consistent with the long-term objective of our research program, which is to support translational studies about the relationships between brain structure and function across species. A better understanding of the mechanisms that underlie memory persistence and forgetting can lead to greater insight into how the brain optimizes memory function. This research program will provide the opportunity for trainees at all levels to acquire a broad range of research knowledge and technical skills. By uniting brain-wide network modelling, assessment of behaviour, genetic models that allow for manipulation of myelin, and MRI, this program will facilitate the acquisition of inter-disciplinary expertise that will prepare trainees for careers in neuroscience or biomedical research both within and outside of academia.

一个健康的大脑会让重要的记忆长久存在，让大多数日常经历被遗忘。伴随着学习而建立的全脑范围的协调神经细胞激活网络，这些网络被稳定以支持持久记忆，而被破坏以导致遗忘。可塑性大脑的变化能力对于网络的形成、稳定和不稳定是必不可少的。大多数研究的重点是神经细胞之间连接点水平的可塑性，在那里可以加强或削弱现有的连接，以及增加或取消以形成新的网络或重塑现有的网络。轴突是神经细胞的细长投影，它传导电脉冲，并允许网络内大脑区域之间的信息整合。此信息的准确计时对网络稳定性至关重要。髓鞘是大脑中支持细胞的一种成分，它将轴突隔绝，因此髓鞘形成的程度将影响电脉冲的产生时间。髓鞘形成始于子宫，经过儿童和青春期，最近的研究表明，髓鞘在成年后一直在变化。这揭示了髓鞘持续可塑性变化对网络稳定性和记忆持久性的影响尚不清楚。拟议的研究将集中在成年期髓鞘发育过程中髓鞘变化和髓鞘重塑对记忆持久性和恐惧记忆网络稳定性的影响，短期目标如下：1.表征全脑髓鞘变化在恐惧记忆持久性中的作用。2.建立全脑髓鞘变化对恐惧记忆网络稳定性影响的计算机模拟模型。如果这里描述的短期目标支持髓鞘可塑性通过网络稳定性在记忆持久性中扮演特定角色，许多方法可以转化为我们实验室的人类研究。这与我们研究计划的长期目标是一致的，即支持关于跨物种大脑结构和功能之间关系的翻译研究。更好地理解记忆持久和遗忘背后的机制，可以更深入地了解大脑是如何优化记忆功能的。这项研究计划将为各级学员提供获得广泛研究知识和技术技能的机会。通过将全脑网络建模、行为评估、允许操作髓鞘的遗传模型和核磁共振相结合，该计划将促进获得跨学科的专业知识，为学员在学术界内外从事神经科学或生物医学研究做好准备。