A role of oligodendrocytes in information processing independent of conduction velocity

Abstract

41Myelinating oligodendrocytes enable fast impulse propagation along axons as revealed 42 through studies of homogeneously myelinated white matter tracts. However, gray matter 43 myelination patterns are different, with sparsely myelinated sections leaving large 44 portions of the axons naked. The consequences of this patchy myelination for 45 oligodendrocyte function are not understood but suggest other roles in information 46 processing beyond the regulation of axonal conduction velocity. Here, we analyzed the 47 contribution of myelin to auditory information processing using paradigms that are good 48 predictors of speech understanding in humans. We compared mice with different degrees 49 of dysmyelination using acute cortical multiunit recordings in combination with behavioral 50 readouts. We identified complex alterations of neuronal responses that reflect fatigue and 51 temporal acuity deficits. Partially discriminable but overall similar deficits were observed 52 in mice with oligodendrocytes that can myelinate but cannot fully support axons 53 metabolically. Thus, myelination contributes to sustained stimulus perception in 54 temporally complex paradigms, revealing a role of oligodendrocytes in the CNS beyond 55 the increase of axonal conduction velocity. 56 65 66Importantly, at the network level, the contribution of CNS myelination to information 67 processing remains poorly understood, in part because suitable phenotyping instruments 68 have been lacking. Yet, there is an increasing awareness that myelination is required for 69 higher-order brain functions. Subtle defects of the white matter have been associated with 70 various psychiatric diseases 6 . Moreover, in the aging brain, the physiological decline of 71 function is associated with subtle but widespread structural deterioration of myelin 7,8 . 72Functional studies of myelin have largely been restricted to motor behavior, which is 73 under control of myelinated axons in white matter tracts, and to the fast impulse 74 propagation and millisecond precision required for sound location in a highly specialized 75 circuit of the brain stem 9 . However, myelin is also present within the cortical grey matter, 76 where it is heterogeneous and patchy along projection neurons 10,11 . Moreover, a large 77 fraction of the parvalbumin-positive interneuron axons are myelinated 12-14 , even though 78 their typical short distance to their target cells has been estimated to cause insignificant 79 conduction delay times 13 . Oligodendrocyte lineage cells can myelinate axons in an 80 activity dependent manner and influence their conduction velocity properties [15][16][17][18][19] . Mature 81 oligodendrocytes respond to glutamatergic signals with enhanced glycolytic support of 82 the axonal energy metabolism 4,5 . These data are compatible with the idea that myelin 83 function in the CNS that go beyond regulating conduction velocity. 85Indeed, there is still a major conceptual gap between the role of myelin in saltatory 86 impulse propagation and its function ...

Auditory impairment in H‐ABC tubulinopathy

“…Longer latencies from wave II found in our mutant model reflect desynchronization of the input at central auditory pathways and nuclei (Roncagliolo et al, 2000). The same results were found in other models of demyelination (Moore et al, 2019). Normal wave I, both in our patient and in the tubulin mutant taiep rat, as well as the comparable thresholds between the tubulin mutant and controls, can be explained by the integrity of the inner ear, which we corroborated by morphology and normal DPOAEs.…”

“…Finally, an additional function of oligodendrocytes is the metabolic support of myelinated axons (Moore et al, 2019). This role becomes even more important when axons spike at higher frequencies.…”

Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

“…While both astrocytes and oligodendrocytes display projections from their cell bodies, those from oligodendrocytes specifically construct the myelin sheath around nearby neurons, a concentric wrapping that improves neuron repolarization and conduction speeds. Additionally, recent literature has demonstrated that oligodendrocyte myelination is not only distinct to single groups of neurons but also exhibits control over synaptic activity and can even manipulate information processing [ 45 , 46 , 47 ]. Microglia are the resident innate immune cells in the CNS, responding to pathogens and injury and clearing dead cells.…”

Myelin Plasticity and Repair: Neuro-Glial Choir Sets the Tuning

“…Newly added myelin sheaths could further provide metabolic support to axons (Fünfschilling et al, 2012;Meyer et al, 2018), the metabolic supply being regulated by neuronal activity (Saab et al, 2016). This myelin addition probably would not result in a global energetic advantage (Harris and Attwell, 2012), but might be needed to generate fast-spiking firing discharges and thus allow for precise axonal firing (Micheva et al, 2016;Moore et al, 2019).…”