Demande de photocopie

Master de Sciences et Technologies
Mention Biologie Intégrative et Physiologie
Spécialité : Neurosciences
Responsable : Professeur Régis LAMBERT
Proposition de Stage M2 S4 NEUROSCIENCES
Année Universitaire 2016-2017
1. Equipe d’Accueil de Master (EAM) :
Intitulé et numéro de l’Unité : Neurophysiology and Nouvelles Microscopy Laboratories
Nom du Responsable de l’Unité : Serge Charpak
Nom du Responsable de l’Équipe : Maria Cecilia Angulo
Intitulé de l’équipe d’accueil : Physiology of NG2 cells
Adresse : Université Paris Descartes, 45, rue des Saints-Pères, 75006 Paris
Nom du responsable de l’encadrement : Maria Cecilia Angulo
Tél. : 0170649935
Fax. : 0142864151
E-mail : [email protected]
2. Titre du sujet :
Using optogenetics to investigate the glutamatergic synaptic connectivity between
neurons and glial progenitors in demyelinating diseases
3. Description du sujet :
Synapses in the brain are not seen today as a property exclusive of neurons. In the last decade, several
studies have shown the presence of functional synapses onto oligodendrocyte precursor cells, also named
NG2 cells, throughout the brain. NG2 cells constitute a major source of remyelinating oligodendrocytes
in demyelinating diseases. It has been speculated that glutamatergic synaptic transmission onto NG2 cells
might regulate proliferation and differentiation of these cells, and thus possibly influences myelin repair.
However, our understanding of how neurons signal to NG2 cells in the injured brain is limited.
Our team recently showed that neuron-NG2 cell synaptic properties are altered in demyelinated lesions of
the mouse and in multiple sclerosis lesions of human tissue. During this Master 2 training, we will
evaluate the balance of synaptic and extrasynaptic signalling mechanisms that may be involved in neuronNG2 cell communication following demyelination. We will combine patch-clamp recordings with a novel
optogenetic approach allowing for targeted stimulation of axons with light in acute slices of corpus
callosum. We already generated a double transgenic mouse in which NG2 cells express DsRed and a
subset of callosal axons express the photosensitive protein channelrhodopsin 2 (ChR2). A local
demyelinating lesion will be induced in these animals in vivo by stereotaxic injection of lysolecithin
within the adult corpus callosum. Then, NG2 cells will be recorded in corpus callosum slices at 7 and 14
days post injection (dpi) and compared to controls. Light pulses will be applied close to the lesion to
photoactivate ChR2/YFP+ axons while recording NG2 cells with a patch pipette. Electrophysiological
and pharmacological analyses will allow us to unravel the balance between synaptic and extrasynaptic
transmission modes between callosal axons and NG2 cells at time points correlating with proliferation
and differentiation of NG2 cells in lesions. This project is part of a more general program for a PhD thesis
that aims to establish how axonal glutamate release influences oligodendrogenesis and myelin repair.
Three recent publications of the team:
Master de Sciences et Technologies
Mention Biologie Intégrative et Physiologie
Spécialité : Neurosciences
Responsable : Professeur Régis LAMBERT
1. 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 (*Co-first authors)
2. Sahel, A*, Ortiz, FC*, Kerninon, C, Maldonado PP, Angulo MC#, Nait Oumesmar B# (2015)
Alteration of synaptic connectivity of oligodendrocyte precursor cells following demyelination. Front
Cell Neurosci, 9:77. (*Co-first authors; #Co-last authors)
3. 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.