Spontaneous Local Calcium Transients Regulate Oligodendrocyte Development in Culture through Store Operated...

Spontaneous Local Calcium Transients Regulate Oligodendrocyte Development in Culture through Store Operated..., Oligodendrocytes (OLs) insulate axonal fibers for fast conduction of nerve impulses by wrapping axons of the central nervous system (CNS) with compact myelin membranes. Differentiating OLs undergo drastic chances in cell morphology. Bipolar oligodendroglial precursor cells (OPCs) transform into highly ramified multipolar OLs, which then expand myelin membranes that enwrap axons.,

Oligodendrocytes (OLs) insulate axonal fibers for fast conduction of nerve impulses by wrapping axons of the central nervous system (CNS) with compact myelin membranes. Differentiating OLs undergo drastic chances in cell morphology. Bipolar oligodendroglial precursor cells (OPCs) transform into highly ramified multipolar OLs, which then expand myelin membranes that enwrap axons. While significant progress has been made in understanding the molecular and genetic mechanisms underlying CNS myelination and its disruption in diseases, the cellular mechanisms that regulate OL differentiation are not fully understood. Here, we report that developing rat OLs in culture exhibit spontaneous Ca²⁺ local transients (sCaLTs) in their process arbors in the absence of neurons. Importantly, we find that the frequency of sCaLTs markedly increases as OLs undergo extensive process outgrowth and branching. We further show that sCaLTs are primarily generated through a combination of Ca²⁺ influx through store-operated Ca²⁺ entry (SOCE) and Ca²⁺ release from internal Ca²⁺ stores. Inhibition of sCaLTs impairs the elaboration and branching of OL processes, as well as substantially reduces the formation of large myelin sheets in culture. Together, our findings identify an important role for spontaneous local Ca²⁺ signaling in OL development.

Significance While Ca²⁺ signals regulate a plethora of cellular activities and their spatiotemporal features, the role of Ca²⁺ signaling in oligodendroglia has not been well established. This study identifies a novel form of Ca²⁺ signaling, spontaneous Ca²⁺ local transients (sCaLTs) that play an important role in oligodendroglial development. In addition, this work reveals a new role for store operated Ca²⁺ entry (SOCE) and release in generating sCaLTs and Ca²⁺ signaling in OLs. Together, these findings establish a novel Ca²⁺ mechanism underlying oligodendroglial development.

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