Role of neuronal activity in oligodendroglia function, myelination and myelin repair

Inserm U894 – Centre de psychiatrie et neurosciences – Paris

Abstract: Myelination is a critical process required for speeding up action potential conduction and providing physical and metabolic support to axons of vertebrates. In the CNS, myelin sheaths are produced by oligodendrocytes (OLs), a glial cell type generated by oligodendrocyte precursor cells (OPCs) during development and in demyelinating diseases. Interestingly, OPCs are the only non-neuronal cells of the CNS that are contacted by bona fide synapses from neurons, but the role of these neuron-glia synapses are still elusive. In addition, increasing evidence suggests that myelination is modulated by neuronal activity and experience, even in the adulthood, allowing for an increased plasticity of neuronal networks. However, the signaling mechanisms regulating OPC and OL function are still poorly understood.
Previous findings of our team demonstrated that OPCs receive a major synaptic input from GABAergic interneurons during postnatal development of the somatosensory cortex. In the first part of the seminar, I will describe our recent studies using electrophysiology and imaging techniques in different transgenic mouse models to unravel the functional properties and role of these GABAergic neuron-glia synapses of the brain. I will mainly focus on a recent work showing that a subpopulation of OPCs forms postnatal functional clusters with GABAergic interneurons arisen from the same embryonic origin.
Despite the low regenerative capacity of the CNS, a production of newly-formed OLs and a partial myelin repair can occur in demyelinating diseases such as Multiple Sclerosis. This OL regeneration depends mostly on the ability of oligodendrocyte precursor cells (OPCs) to proliferate and differentiate into the site of damage. In the second part of the talk, I will present our recent findings showing how neuronal activity in vivo enhances functional myelin repair in demyelinated lesions using an optogenetic approach.

Invited by Rosa COSSART