Fig. 9: Oligodendrocyte lineage cells display distinct baseline and norepinephrine-evoked Ca²⁺ signals during proliferation and differentiation.

OPCs sense neurotransmitters (e.g., Glutamate, GABA) and neuromodulators (NE) at the OPC-axon junctions. During the resting phase (R: when mouse did not engage in exploratory behavior), the Ca²⁺ activity of oligodendrocyte lineage cells (OPCs, pmOL1, pmOL2 and OLs) is mainly driven by the baseline neuronal activity in the cortex. As OPCs differentiate into pmOL2 and OL the baseline activity is significantly reduced (see Ca²⁺ activity indicator bars). During arousal, when mouse is alert and engages into exploratory bouts of locomotion (A: active phase), NE is released from cortical projections of LC neurons, which enhanced the Ca²⁺ activity in OPCs and pmOL1, but not in pmOL2 an OLs. About 30% of OPCs do not show increased Ca²⁺ activity in response to locomotion and preferentially proliferate – we called these OPCs Locomotion Non-Responsive (LNR-OPCs). A newly born daughter OPCs has half the baseline activity of the mother cell, and also does not respond to locomotion (see Resting side, left). OPC population which responded to exploratory locomotion bouts by increasing frequency of Ca²⁺ transients are more likely to differentiate into pmOLs and later mature into OLs - we called them Locomotion Responsive OPCs (LR-OPCs). Chemogenetic activation LC-neurons to release NE or a direct increase in OPCs Ca²⁺ signals promoted the differentiation of OPCs into mature OLs. Part of the illustration was created using BioRender.