Glucocorticoids target postnatal oligodendrocyte precursor cells to modulate adult hippocampal network plasticity and stress-induced behavior
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Aversive early experiences affect brain development and enhance the risk of psychiatric disorders. Recent evidence has implicated oligodendrocyte precursor cells (OPCs) in the pathophysiology of stress-related diseases. Beside their myelination-dependent functions, OPCs are involved in the fine-tuning of neuronal activity and responding to environmental challenges. OPCs express the glucocorticoid receptor (GR) binding glucocorticoids (GCs) and are sensitive to aversive experiences. To decipher the role of early postnatal GCs on OPC maturation, neuronal network activity and adult behavior we conditionally deleted GR in postnatal OPCs. Such deletion resulted in a reduction of oligodendrocytes in the hippocampus, alteration of hippocampal network activity and impairment in the formation of memories in adulthood. Our findings reveal a novel role for postnatal GRs in modulating OPC maturation, neuronal network excitability and adult memory formation. This provides the first evidence for a dual role of GR signaling in both the canonical and non-canonical functions of OPCs.
