Effect of increased neuronal activity on myelin repair in freely moving mice using optogenetics
Dates:2 January 2018 - 29 June 2018
Date limite de candidature:29 June 2018
~ Jan-March 2018 (To be discussed)
~ April-June 2018
Myelinating oligodendrocytes (OLs) in the brain are generated from oligodendrocyte precursor cells (OPCs), named NG2 cells. OPCs also constitute a major source of remyelinating OLs in demyelinating diseases such as Multiple Sclerosis. Remyelination failure in this disease is a characteristic of long-standing and primary progressive lesions and is associated with defects in action potential conduction. It has been established that normal myelination depends on neuronal activity, but a role of electrical activity in myelin repair is still unclear. In addition, the underlying mechanisms linking neuronal activity with oligodendroglia proliferation, differentiation and myelin production are elusive. In this project, we will evaluate the influence of the activity of demyelinated axons on oligodendrogenesis and myelin repair in vivo by using an optogenetic approach. To test this possibility, we will perform lysolecythin (LPC)-induced demyelinating lesions in corpus callosum of Thy1-ChR2-YFP transgenic mice which express the light sensitive protein channelrhodopsin-2 (ChR2) in a subset of callosal axons. The model is already well established in the laboratory and the student will need to learn mouse brain surgery, in vivo optogenetic stimulation, electrophysiology, immunostainings and confocal imaging. We will elucidate the effect of increased axonal activity on oligodendrocyte regeneration in freely moving mice. The effect of photostimulation on oligodendrogenesis and remyelination is assessed in perfused animals by immunostainings using specific markers for oligodendroglia lineage cells. Second, we will examine whether photo-activated ChR2-expressed axons are preferentially remyelinated by using immunostainings against MBP or other myelin markers. Our results may open new perspectives to manipulate in vivo oligodendroglia development by using controlled neuronal stimulation in demyelinating lesions.
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