UCSF

Experience-dependent myelination is hypothesized to shape neural circuit function and subsequent behavioral output. Using a contextual fear memory task in mice, we demonstrate that fear learning induces oligodendrocyte precursor cells (OPCs) to proliferate and differentiate into myelinating oligodendrocytes (OLs) in the medial prefrontal cortex (mPFC). Transgenic animals which cannot form new myelin exhibit deficient remote, but not recent, fear memory recall. Recording population calcium dynamics with fiber photometry, we observe that the neuronal response to conditioned context cues evolves over time in the mPFC, but not in animals that cannot form new myelin. Finally, we demonstrate that pharmacological induction of new myelin formation with clemastine fumarate improves remote memory recall and promotes fear generalization. Thus, bidirectional manipulation of myelin plasticity functionally impacts behavior and neurophysiology, suggesting that neural activity during fear learning instructs the formation of new myelin, which, in turn, supports the consolidation and/or retrieval of remote fear memories.