Neuroglial Interactions in Cerebral Physiopathology

Leader

Research center

11 place Marcelin Berthelot
75231 Paris
Serge Haroche

Institution

Collège de France
CNRS
Inserm
ED158
Université Pierre et Marie Curie

Laboratory

Centre Interdisciplinaire Recherche Biologie
UMR7241 - U1050
Labex Memolife

Keywords

astrocytes
neuroglial
Available to host a PhD student

Publications

Chever O, Dossi E, Pannasch U, Derangeon M, Rouach N. Astroglial networks promote neuronal coordination. Sci Signal. 2016 Jan 12;9(410):ra6. doi: 10.1126/scisignal.aad3066.

Pannasch U, Freche D, Dallérac G, Ghézali G, Escartin C, Ezan P, Cohen-Salmon M, Benchenane K, Abudara V, Dufour A, Lübke JH, Déglon N, Knott G, Holcman D, Rouach N. Connexin 30 sets synaptic strength by controlling astroglial synapse invasion. Nat Neurosci. 2014 Apr;17(4):549-58. doi: 10.1038/nn.3662. Epub 2014 Mar 2.

D. Freche, U. Pannasch, N. Rouach, D. Holcman. Synapse geometry and receptor dynamics modulate synaptic strength. PLoS One. 6: e25122. 2011

U. Pannasch, L. Vargova, J. Reingruber, P. Ezan, D. Holcman, C. Giaume, E. Sykova, N. Rouach. Astroglial networks scale synaptic activity and plasticity. PNAS (USA). 108: 8467-72.2011.

T. Mehmood*, A. Schneider*, J. Sibille, P. Marques Pereira, S. Pannetier, M. Ammar, D. Dembele, C. Thibault-Carpentier, N. Rouach, A. Hanauer. Transcriptome profile reveals AMPA receptor dysfunction in the hippocampus of the Rsk2-knockout mice, an animal model of Coffin-Lowry Syndrome. Human Genetics. 129: 255-69.2011.

C. Giaume, A. Koulakoff, L. Roux, D. Holcman, N. Rouach Astroglial networks: a step further in neuroglial and gliovascular interactions. Nature Reviews Neuroscience. 11: 87-99. 2010.

N. Rouach Astroglial connexins fuel synapses. Medecine Sciences . 25: 102-4. 2009.

N. Rouach, A. Koulakoff, V. Abudara, K. Willecke, C. Giaume. Astroglial metabolic networks sustain hippocampal synaptic transmission. Science . 322:1551-5. 2008.

Fields of research

Neurophysiology / systems neuroscience

Research Theme

The main goal of our group is to determine whether and how astrocytes play an active and direct role in information processing. We want to unravel the molecular modalities and functional outcomes of neuroglial interactions in physiological and pathological conditions. More precisely, we want to understand how neurons and glia communicate in various regimes of activity and determine the outcome of disrupting their communication on neuronal functions, including their excitability, synaptic transmission, plasticity and synchronization. To overcome the present conceptual and experimental difficulties in the field of neuroglial interactions, we have developed a challenging novel interdisciplinary approach combining electrophysiology, imaging, molecular biology, biochemistry, mathematical modeling and new pharmacological strategies and molecular tools targeted to astrocytes, which permit to analyze and act selectively on populations of astrocytes. Indeed, a particularly original aspect of our research in this field consists in using tools targeting specifically astrocytes: either pharmacological tools, delivered intracellularly in single astrocytes through a patch pipette and then diffusing in the gap-junction mediated network, or molecular tools, such as knockout mice for astrocytic proteins, as well as more recently, novel engineered lentiviral vectors targeting specifically astrocytes (collaboration with N. Déglon/C. Escartin, MIRCen). Using this multidisciplinary and innovative strategy, our goal is to decipher the specific role of key astroglial properties, such as calcium signaling, membrane currents, as well as connexin and pannexin-mediated transmission in basal synaptic activity, synaptic plasticity, synchronous physiological and pathological (epilepsy) activities.

Lab rotation

Role of astrocytes in the formation and remodeling of synaptic circuits

Team leader: 

ROUACH Nathalie

Dates: 

September 18, 2017 - December 22, 2017

Application deadline: 

December 22, 2017

Period

~ Sept-Dec 2017

Project

Recent data point to a key role of astrocytes in controlling synapse formation, maturation, activity and elimination. The visual cortex is a hallmark brain region of experience-dependent developmental shaping of synaptic circuits during the critical period of enhanced plasticity that follows eyes opening. Physical removal and/or shaping of synapses implies morphological alterations, which may well be influenced by astroglial perisynaptic processes. Strikingly, we have recently shown that the gap junction protein connexin 30 (Cx30), besides forming channels, regulates synaptic transmission via an unconventional non-channel function, by preventing astrocytes to penetrate synaptic clefts. 

This rotation project will determine whether astroglial Cx30, of which developmental expression coincides with the closing of the critical period, is involved in experience dependent modeling of cortical networks during development.

Contact

Collège de France - CIRB - 11, place Marcelin Berthelot 75005 Paris - +33 1 44 27 14 49 - Nathalie.rouach@college-de-france.fr

Supervisor: 

ROUACH Nathalie