How Do Cells of the Oligodendrocyte Lineage Affect Neuronal Circuits to Influence Motor Function, Memory and Mood?

Abstract

Oligodendrocyte progenitor cells (OPCs) are immature cells in the central nervous system (CNS) that can rapidly respond to changes within their environment by modulating their proliferation, motility and differentiation. OPCs differentiate into myelinating oligodendrocytes throughout life, and both cell types have been implicated in maintaining and modulating neuronal function to affect motor performance, cognition and emotional state. However, questions remain about the mechanisms employed by OPCs and oligodendrocytes to regulate circuit function, including whether OPCs can only influence circuits through their generation of new oligodendrocytes, or can play other regulatory roles within the CNS. In this review, we detail the molecular and cellular mechanisms that allow OPCs, newborn oligodendrocytes and pre-existing oligodendrocytes to regulate circuit function and ultimately influence behavioral outcomes.

Low‐intensity transcranial magnetic stimulation promotes the survival and maturation of newborn oligodendrocytes in the adult mouse brain

“…Myelinating oligodendrocytes are added to the central nervous system (CNS) throughout life, generated from immature, proliferative oligodendrocyte progenitor cells (OPCs), also known as NG2‐glia (reviewed by Pepper, Pitman, Cullen, & Young, ). In development and adulthood, myelination is regulated by many intrinsic and extrinsic factors, with neuronal activity being a major extrinsic regulator of adaptive myelination (reviewed by Bechler, Swire, & Ffrench‐Constant, ), influencing OPC proliferation (Barres & Raff, ; Gibson et al, ), oligodendrogenesis (Gibson et al, ; Li, Brus‐Ramer, Martin, & McDonald, ), oligodendrocyte survival (Barres, Jacobson, Schmid, Sendtner, & Raff, ; Kougioumtzidou et al, ), myelin sheath stabilization (Hines, Ravanelli, Schwindt, Scott, & Appel, ), the number of internodes supported per oligodendrocyte (Mensch et al, ), and myelin sheath thickness (Gibson et al, ).…”

Severe hydroxymethylbilane synthase deficiency causes depression-like behavior and mitochondrial dysfunction in a mouse model of homozygous dominant acute intermittent porphyria

“…Indeed, evidence from previous animal studies, post-mortem human studies, as well as genetic and neuroimaging experiments indicate an association between major depressive disorder (MDD) and changes in brain myelin content [54]. Interestingly, patients with neurological disorders of the white matter, like multiple sclerosis (MS) often show psychiatric symptoms, including depression, and display comparable dysregulation in gene expression [55,56]. In line with our observations, myelin deficits have been revealed in the seminal characterization of the (HD-AIP) KI mice [13] and have also been reported in AIP patients [57].…”

Periaxonal and nodal plasticity modulate action potential conduction in the adult mouse brain

“…Within the central nervous system (CNS), oligodendrocytes elaborate myelin internodes to facilitate the rapid and saltatory conduction of action potentials and to provide vital trophic support to axons via the periaxonal space (1). During development, the extension and retraction of internodes is regulated by neuronal activity and calcium signaling within the nascent myelin 5 sheaths [reviewed in (2)], and after maturation, oligodendrocytes retain some capacity to lengthen or shorten their internodes (3,4). However, the extent to which mature oligodendrocytes can adapt, when the pattern of neuronal activity is altered, to dynamically modulate action potential conduction has not been explored.…”

“…However, iTBS subtly changed myelin structure. Anchoring proteins expressed within the myelin loops of each internode interact with the axonal proteins contactin and contactin-associated protein 20 (Caspr) to form paranodes that maintain voltage-gated sodium channels (NaV1.6) at the nodes of Ranvier [reviewed in (2)]. We immunolabeled coronal brain sections to visualize the nodes of Ranvier (NaV1.6) that were clearly flanked by two abutting paranodes (Caspr) (Figure 1A-D), and found that iTBS shifted the node length distribution towards shorter nodes within M1 (Figure 1E) and the CC (Figure 1F).…”

“…Patterns of neuronal activity can also be physiologically altered through learning, and motor learning has been shown to promote oligodendrogenesis and increase myelination of active neural circuits [reviewed in (2)]. To investigate this, we exposed mice to spatial learning training in the radial arm maze (Figure S4), to increase neuronal activity in the hippocampus, and then examined 20 node length in the fimbria, a major output tract of the hippocampus.…”