Interactions between neurons and oligodendroglia in myelination and myelin repair

Research center

Institution

Inserm
Université Paris Descartes
ED157 GC2ID

Laboratory

Neurophysiology & New Microscopies Laboratory
Phone: (+33) 1 70 64 99 35
U894

Mots clefs

Patch clamp
Optogenetics
Available to host a PhD student

publications

Balia M*, Vélez-Fort M*, Passlick S, Schäfer C, Audinat E, Steinhäuser C, Seifert G, Angulo MC (2015) Postnatal down-regulation of the GABAA receptor 2 subunit in neocortical NG2 cells accompanies synaptic-to-extrasynaptic switch in GABAergic transmission mode. Cereb Cortex, 25(4):1114-23

Balia M, Benamer N, Angulo MC (2017) A specific GABAergic synapse onto oligodendrocyte precursors does not regulate cortical oligodendrogenesis. Glia. 65(11):1821-1832.

Ledonne F, Orduz D, Mercier J, Vigier L, Grove EA, Tissir F, Angulo MC, Pierani A*, Coppola E*. (2016) Targeted inactivation of Bax reveals subtype-specific mechanism of Cajal-Retzius neuron death in the postnatal cerebral cortex. Cell Rep. 17(12) 3133

Wake H*, Ortiz FC*, Woo DH, Lee P, Angulo MC, Fields D (2015) Non-synaptic junctions on myelinating glia promote preferential myelination of electrically-active axons. Nat Commun 6:7844

Orduz D*, Maldonado PP*, Balia M, Vélez-Fort M, de Sars V, Yanagawa Y, Emiliani V, Angulo MC (2015) Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex. eLife 4:e06953

 

Fields of research

Neurophysiology / systems neuroscience

Research Theme

Oligodendrocyte precursor cells expressing the chondroitin sulfate proteoglycan NG2, also called NG2 cells, have the ability to proliferate in the postnatal brain to generate oligodendrocytes in grey and white matters. NG2 cells play a critical role in myelination during postnatal brain development, but a pool of these progenitors is maintained in the adult and recruited to lesions in demyelinating diseases. Recent discoveries have demonstrated that NG2 cells are contacted by functional glutamatergic and GABAergic synapses from neurons in grey and white matters. The function of these synapses is still elusive. Our group is interested in the functional properties and role of neuron-NG2 cell synapses as well as in exploring new neuronal signaling mechanisms controlling NG2 cell activity in the normal and injured brains. Our research program consists of studying these synapses in the somatosensory cortex (grey matter) and corpus callosum (white matter) to dissect the synaptic connectivity of NG2 cells and decipher whether neuronal synaptic inputs control NG2 cell fate in an activity-dependent manner. We use a multidisciplinary approach that combines patch-clamp recordings, calcium imaging, immunostaining techniques, optogenetics and advanced optical methods to analyze NG2 cell physiology in acute slices and in vivo during postnatal development and a demyelination/remyelination process. Our studies may bring new perspectives on the roles played by NG2 cells in the brain and for the design of innovative therapies promoting myelin repair in demyelinating diseases.

Lab rotation

Effect of increased neuronal activity on myelin repair in freely moving mice using optogenetics

Chercheur responsable: 

ANGULO Maria Cecilia

Dates: 

2 January 2018 - 29 June 2018

Date limite de candidature: 

29 June 2018

Period

~ Jan-March 2018 (To be discussed)

~ April-June 2018 

Project

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.

Contact

New Center of Psychiatry and Neurosciences - 102 Rue de la Santé 75014 Paris - maria-cecilia.angulo@parisdescartes.fr

Superviseur: 

ANGULO Maria Cecilia