Impact of myelin dynamics on functional network stability and memory persistence

一个健康的大脑会让重要的记忆持续很长时间，而大多数日常经历会被遗忘。在学习过程中，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——大脑改变的能力——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水平的可塑性，在这里，现有的连接可以加强或削弱，也可以增加或消除，以形成新的网络或改造现有的网络。***轴突是神经细胞的细长突起，它可以传导电脉冲，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网络的稳定性至关重要。髓鞘是大脑中支持细胞的一种成分，它隔离轴突，因此髓鞘形成的程度会影响电脉冲的时间。髓鞘形成始于子宫，贯穿童年和青春期，最近的研究表明髓鞘在成年期继续变化。这揭示了持久可塑性的另一个因素——髓磷脂的变化——其对网络稳定性和记忆持久性的影响尚不清楚。***拟开展的研究将集中在髓磷脂的变化——发育过程中的髓磷脂形成和成年期髓磷脂重塑——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。描述全脑髓磷脂变化在恐惧记忆持久性中的作用。2. 在计算机模拟中模拟全脑髓磷脂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为髓磷脂可塑性通过网络稳定性在记忆持久性中的特定作用提供了支持，那么我们实验室的许多方法都可以转化为人类研究。这与我们研究项目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和遗忘背后的机制可以让我们更深入地了解大脑是如何优化记忆功能的。***该研究项目将为各级受训者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、允许操纵髓磷脂的遗传模型和MRI结合起来，该项目将促进跨学科专业知识的获取，为学术界内外的神经科学或生物医学研究领域的学员做好准备。**

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.**