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: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=668447
• 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持续很长一段时间，而大多数日常经历都会被遗忘。协调神经细胞激活的全脑网络的建立伴随着学习，这些网络被稳定以支持持久记忆，而不稳定则导致遗忘。可塑性-大脑的变化能力-对于网络的形成，稳定和不稳定至关重要。大多数研究的重点是神经细胞之间连接点的可塑性，现有的连接可以加强或削弱，以及增加或消除以形成新的网络或重塑现有网络。* 轴突是神经细胞的细长突起，传导电脉冲，并允许网络内大脑区域之间的信息整合。这些信息的精确定时对于网络稳定性至关重要。髓鞘是大脑中支持细胞的一种成分，它使轴突绝缘，因此髓鞘形成的程度将影响电脉冲的时间。髓鞘形成始于子宫，并在儿童和青少年时期发展，最近的研究表明，髓鞘在成年期不断变化。这揭示了持久可塑性的另一个因素-髓鞘的变化-其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髓鞘变化的影响-髓鞘形成在发展和重塑髓鞘在成年期-对记忆的持久性和稳定性的恐惧记忆网络与以下短期目标：1。描述全脑髓鞘变化在恐惧记忆持续性中的作用。2.在计算机模拟中模拟全脑髓鞘变化对恐惧记忆网络稳定性的影响。如果这里描述的短期目标通过网络稳定性为髓鞘可塑性在记忆持久性中的特定作用提供支持，那么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，即支持跨物种大脑结构和功能之间关系的转化研究。更好地理解记忆持久性和遗忘的机制可以更好地了解大脑如何优化记忆功能。* 该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。通过统一全脑网络建模，行为评估，允许操纵髓鞘的遗传模型和MRI，该计划将促进跨学科专业知识的获取，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。