26 August 2015

Physiology of NG2 cells

PI : Maria Cecilia ANGULO

Members : Najate BENAMERChloé HABERMACHER, Blandine MANOT-SAILLETManon OMNES,

3D reconstruction of a biocytin-labelled NG2 cell

3D reconstruction of a biocytin-labelled NG2 cell

The principal function of oligodendrocytes in the central nervous system (CNS) is to produce the myelin sheath that insulate axons and increase the conduction velocity of action potentials. The process of myelination occurs progressively during development of humans and rodents and continues through juvenile stages. Oligodendrocytes derive from oligodendrocyte precursor cells expressing the proteoglycan NG2, also called NG2 cells, a class of progenitors in the CNS highly abundant at birth, but also persistent in the adult. By their capacity to generate oligodendrocytes, NG2 cells play a central role in myelination during postnatal development. However, their large abundance and widespread distribution suggest that, in addition to progenitors, NG2 cells reside in the mature brain to play other functions. NG2 cells are thus multifaceted cells that influence brain development and function. In addition, since they are a main pool of progenitors in young and adult stages, they constitute an important therapeutic target.

In the CNS, chemical synapses are specialized cellular junctions allowing neurons to transfer the information that underlies perception and cognition. However, synapses in the brain are not a property exclusive of neurons in the brain. In the past decade, it has been demonstrated the existence of functional glutamatergic and GABAergic synapses between neurons and NG2 cells. Our group is interested in understanding the functioning and role of these synapses as well as new neuronal signaling mechanisms that control the activity of NG2 cells during development and in the adult brain.

Our strategy consists in using a multidisciplinary approach that combines patch-clamp recordings, calcium imaging, immunostaining techniques, optogenetics and advanced optical methods to analyze NG2 cell physiology during postnatal development and after 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.

Our projects are articulated around two different axes:

  1. Channels, receptors and GABAergic synapses of NG2 cells in the developing somatosensory cortex
  2. Channels, receptors and glutamatergic synapses of NG2 cells in the adult corpus callosum after a demyelinating lesion

Postdoctoral position available : candidates should send a CV, a letter of motivation and the name of 2-3 referees to Maria Cecilia ANGULO.

Publications

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

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.

Maldonado, PP, Angulo, MC (2015) Multiple modes of communication between neurons and oligodendrocyte precursor cells. Neuroscientist 21(3):266-76 (Invited review)

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 Gamma2 subunit in neocortical NG2 cells accompanies synaptic-toextrasynaptic switch in GABAergic transmission mode. Cereb Cortex25(4):1114-23

Maldonado PP, Vélez-Fort M, Levavasseur F, Angulo MC (2013) Oligodendrocyte precursor cells are accurate sensors of local K+ in mature gray matter. J Neurosci 30(20):33(6):2432-42

M. Vélez-Fort, E. Audinat, M. C Angulo, 2011. The central role of GABA in neuron-glia interactions. Neuroscientist. Online first.

P. P Maldonado, M. Vélez-Fort, M. C Angulo, 2011. Is neuronal communication with NG2 cells synaptic or extrasynaptic?. Journal of Anatomy. vol.219. 1. July. 8-17.

Vélez-Fort M, Maldonado PP, Butt AM, Audinat E, Angulo MC (2010) Postnatal switch from synaptic to extrasynaptic transmission between interneurons and NG2 cells. J Neurosci30(20):6921-9