Cell-type, circuit and network mechanisms of adult oligodendrogenesis in memory storage and retrieval

项目总结 少突胶质前体细胞在成人脑内始终持续产生有髓少突胶质细胞。 生活。成人大脑回路的活跃髓鞘形成已被证明对某些形式的学习很重要，而且 我们小组最近的研究表明，这是记忆存储和检索中的一个关键过程。然而， 虽然以前的工作为成人大脑中髓鞘可塑性的调节提供了必要的见解，但它是 不清楚这一过程如何影响记忆电路内神经编码的动态性质。髓鞘形成 提高单个轴突的传导速度，但这将如何转化为在 对神经回路及其随后的行为输出的了解甚少。因此，有相当大的差距 那些与成人轴突髓鞘形成有关的发现和那些描述神经的发现之间存在着差异 编码动态是记忆编码、巩固和回忆的基础。在这项提案中，我们的目标是架起 这一缺口通过1)阐明了小鼠内侧前额叶皮质中在一段时间后变成有髓鞘的细胞类型 学习经验，2)决定大脑皮质回路活跃的髓鞘形成如何影响细胞编码 支持记忆，3)依赖活动的髓鞘形成如何调节同步性和区域间 恐惧记忆回忆过程中内侧前额叶皮质、杏仁核和海马区之间的联系 4)少突胶质细胞前体在体内增殖分化的时间动态 内存编码。这些研究将首次为新技术之间的双向相互作用提供证据 髓鞘形成和主动记忆编码集合，将阐明神经胶质细胞的基本机制 在学习和记忆过程中发出信号。

PROJECT SUMMARY Oligodendrocyte precursor cells continually produce myelinating oligodendrocytes in the adult brain throughout life. Active myelination of adult brain circuits has been shown to be important for some forms of learning, and recent work from our groups has shown that this a crucial process in memory storage and retrieval. However, while previous work has provided essential insight into the regulation of myelin plasticity in the adult brain, it is not clear how this process impacts the dynamic nature of neural encoding within memory circuits. Myelination increases conduction velocity across individual axons, however how this translates to computations at the level of neural circuits and their subsequent behavioral outputs is poorly understood. Thus, a considerable gap exists between those findings related to axonal myelination in the adult and those that describe the neural coding dynamics that underlie memory encoding, consolidation and recall. In this proposal we aim to bridge this gap by 1) elucidating the cell types in the mouse medial prefrontal cortex that become myelinated after a learning experience, 2) determine how active myelination of cortical circuits impacts the cellular codes that support memory, 3) how activity-dependent myelination modulates the synchronization and interregional communication between the medial prefrontal cortex, amygdala and hippocampus during fear memory recall and 4) the temporal dynamics of oligodendrocyte precursor proliferation and differentiation in vivo after memory encoding. These studies will provide the first ever evidence for bidirectional interaction between new myelin formation and active memory encoding ensembles and will elucidate fundamental mechanisms of glial signaling during learning and memory.