Proliferation, differentiation, and glutamatergic synapses: Communication between neurons and oligodendrocyte precursor cells

Abstract

The healthy physiological functioning of the mammalian central nervous system relies on the precise communication between many different cell types. The most general communication channel between neurons is the chemical synapse. Fascinatingly, oligodendrocyte precursor cells also receive synaptic input from glutamatergic neurons. Oligodendrocyte precursor cells are responsible for forming the myelin sheaths by differentiating into oligodendrocytes, and the myelination itself seems to be regulated by neuronal firing patterns. The differentiation and proliferation of oligodendrocyte precursor cells are influenced by transient changes of neuronal firing. Therefore the questions arise: Can oligodendrocyte precursor cells discriminate dissimilar patterns of neuronal firing? How exactly those different patterns would influence their proliferation and differentiation? How the physiological properties of synaptic signaling would influence the cellular behavior of oligodendrocyte precursors? In my doctoral thesis I analyzed in details the synaptic responses of oligodendrocyte precursors to different, repetitive axonal stimulation patterns; and found that the postsynaptic responses are very diverse upon the various patterns of axonal activation. I showed in vivo that these distinct patterns do influence the proliferation and differentiation of oligodendrocyte precursors in a dissimilar way, even though the sum activity and transmitted charge through their synaptic receptors were similar in the applied paradigms. I also demonstrated that the quantal parameters at the axon – OPC synapses are sensitive to the method by which the quantal synaptic events had been triggered. Therefore the different approaches to trigger quantal events are not interchangeable or substitutable with each other. Lastly, with my colleagues we established that the exact physiological parameters of the glutamatergic synaptic transmission matter greatly to these cells: modifications of the AMPA receptors on oligodendrocyte precursors considerably altered their proliferation and differentiation. The results discussed in this thesis not only show how millisecond-scale events, such as synaptic currents, can influence slow biological processes as cell cycle or cell differentiation; but also carry key implications for various myelin-related diseases, for instance multiple sclerosis.