Myelin plasticity: sculpting circuits in learning and memory

Abstract

Throughout our lifespan, new sensory experiences and learning continually shape our neuronal circuits to form new memories. Plasticity at the level of synapses has been recognized and studied for decades, but recent work has revealed an additional form of plasticity - affecting oligodendrocytes and the myelin sheaths they produce - that plays a crucial role in learning and memory. In this Review, we summarize recent work characterizing plasticity in the oligodendrocyte lineage following sensory experience and learning, the physiological and behavioural consequences of manipulating that plasticity, and the evidence for oligodendrocyte and myelin dysfunction in neurodevelopmental disorders with cognitive symptoms. We also discuss the limitations of existing approaches and the conceptual and technical advances that are needed to move forward this rapidly developing field.

Fig. 1 |. Forms of plasticity within the oligodendrocyte lineage.

Oligodendrocyte precursor cells (OPCs) proliferate and a subset of these newly formed OPCs differentiate into new oligodendrocytes^,. Other existing OPCs directly differentiate into new oligodendrocytes^,. A subset of these new oligodendrocytes undergo cell death, whereas others stably integrate into the circuit and form new sheaths on previously unmyelinated axon segments. Existing oligodendrocytes can also undergo plasticity in the form of altered sheath length and thickness^,,, (and, under specific conditions, new sheath generation).

Fig. 2 |. Modulation of neuronal function and plasticity by oligodendroglia and myelin.

Oligodendrocytes express the inward rectifying potassium channel Kir4.1 and participate in extracellular potassium clearance, which can affect neuronal excitability. They also regulate neurotransmitter release and metabolism through the expression of glutamine synthetase and the release of molecules like glutamine and brain-derived neurotrophic factor (BDNF). Differential (and adjustable) myelination patterns can regulate the precise timing of action potential arrival in various circuits^,,,. Manipulating levels of myelination also changes synapse density in development and in ageing^,. Oligodendrocytes and myelin may regulate structural synapse plasticity through Nogo-A. Finally, oligodendrocyte precursor cells (OPCs) may influence circuit activity in myelin-independent ways, such as through cleavage and secretion of NG2 (REF.).