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

成体少突胶质细胞发生在记忆存储和检索中的细胞类型、回路和网络机制

基本信息

批准号：
10606616
负责人：
Jonah R Chan
金额：
$ 69.5万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-02 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10606616
关键词：
Ablation Address Adult Amygdaloid structure Area Axon Behavioral Brain Cells Chronic Code Communication Data Electrophysiology (science)Elements Fright Future Generations Genetic Goals Hippocampus Histologic Immediate-Early Genes Impairment Individual Interneurons Investigation Learning Life Link Measures Medial Memory Microscopy Mus Myelin Nature Neural Inhibition Neurons Oligodendroglia Output Parvalbumins Positioning Attribute Prefrontal Cortex Preparation Process Production Proliferating Regulation Reporting Resolution Retrieval Role Specificity System Techniques Testing Therapeutic Translating Viral Work brain dysfunction cell type entorhinal cortex experience fear memory gene induction improved in vivo in vivo calcium imaging in vivo imaging innovation insight long term memory memory encoding memory recall memory retrieval myelination neural neural circuit neurotransmission novel oligodendrocyte precursor post-traumatic stress precursor cell temporal measurement treatment of anxiety disorders two-photon

项目摘要

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.

项目概要少突胶质细胞前体细胞在成年大脑中不断产生髓鞘少突胶质细胞生活。成人大脑回路的主动髓鞘化已被证明对于某些形式的学习很重要，并且我们小组最近的工作表明，这是记忆存储和检索的关键过程。然而，虽然之前的工作为成人大脑中髓磷脂可塑性的调节提供了重要的见解，但尚不清楚这个过程如何影响记忆电路内神经编码的动态性质。髓鞘形成增加各个轴突之间的传导速度，但这如何转化为该水平的计算人们对神经回路及其随后的行为输出知之甚少。因此，差距相当大与成人轴突髓鞘形成相关的发现与描述神经元轴突髓鞘形成的发现之间存在编码动态是记忆编码、巩固和回忆的基础。在本提案中，我们的目标是架起桥梁这一差距通过 1) 阐明了小鼠内侧前额叶皮层中在经过一段时间后变成有髓鞘的细胞类型。学习经验，2）确定皮质回路的活跃髓鞘形成如何影响细胞代码支持记忆，3）活动依赖性髓鞘形成如何调节同步和区域间恐惧记忆回忆过程中内侧前额叶皮层、杏仁核和海马体之间的交流 4）少突胶质细胞前体增殖和分化后体内的时间动态记忆编码。这些研究将为新生物之间的双向相互作用提供第一个证据。髓磷脂形成和主动记忆编码整体，并将阐明神经胶质细胞的基本机制学习和记忆过程中的信号传递。