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

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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.