Preservation of a remote fear memory requires new myelin formation

• Published in: Nature neuroscience Vol. 23; no. 4; pp. 487 - 499
• Main Authors: Pan, Simon, Mayoral, Sonia R, Choi, Hye Sun, Chan, Jonah R, Kheirbek, Mazen A
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.04.2020
• Subjects: Analysis; Animals; Behavioral plasticity; Calcium; Calcium signalling; Cell differentiation; Cell Proliferation - physiology; Circuits; Conditioning, Classical - physiology; Fear; Fear - physiology; Glial stem cells; Learning; Memory tasks; Memory, Long-Term - physiology; Mental task performance; Mice; Mice, Transgenic; Myelin; Myelin Sheath - physiology; Myelination; Neural plasticity; Neurophysiology; Oligodendrocyte Precursor Cells - physiology; Oligodendrocyte Transcription Factor 2 - genetics; Oligodendrocytes; Photometry; Physiological aspects; Prefrontal cortex; Prefrontal Cortex - physiology; Preservation; Psychological aspects; Recall; Recollection (Psychology); Transgenic animals; United States
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/s41593-019-0582-1

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 to proliferate and differentiate into myelinating oligodendrocytes in the medial prefrontal cortex. Transgenic animals that cannot form new myelin exhibit deficient remote, but not recent, fear memory recall. Recording population calcium dynamics by fiber photometry, we observe that the neuronal response to conditioned context cues evolves over time in the medial prefrontal cortex, 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 affects behavior and neurophysiology, which suggests 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.