Responsable : Nathalie Rouach

Recherche

1Astrocytes play critical roles in brain development, activity and disorders through dynamic interactions with neurons. However, comprehensive molecular description of such modulations is still limited. This last year we investigated the role of several astroglial properties in neurotransmission, including their network organization mediated by gap junction channels (1), potassium uptake by Kir4.1 channels (2) and calcium signaling (3). 1) We have investigated the role of gap-junction mediated astroglial networks in neuronal synchronization (Chever et al., 2016). Using knockout mice for astroglial connexins, we found that astroglial networks promote population bursts in hippocampal slices. Astroglial networks indeed limited neuronal depolarization induced by spontaneous synaptic activity, enhanced release probability, and promoted neuronal recruitment during bursting, thus favoring synchronized activation of neuronal networks. This translated in vivo into an enhanced severity of epileptiform events and convulsive behavior. Altogether, these data reveal that gap-junction mediated astroglial networks coordinate bursting of neuronal ensembles, which aggravates pathological network activity. This study thus provides molecular and biophysical evidence predicting selective inhibitors of astroglial gap junction channels as anticonvulsive drugs. 2) We also examined the role of Kir4.1 channels in the neuroglial potassium cycle during neurotransmission using mathematical modeling and physiology. We found that astrocytes uptake in less than 10 seconds more than 80 % of the neuronal released potassium in response to basal, repetitive and tetanic stimulations, which prevent the generation of epileptiform activity in the hippocampus. We also showed that Kir4.1 channels particularly regulate neuronal excitability for 3-10 Hz rhythmic activity, suggesting an important contribution in theta rhythmic activity. 3) Finally using dual recordings of astroglial calcium signaling and synaptic transmission, we demonstrated that calcium signaling of astrocytes, thought to represent their excitability, shows, concomitantly to excitatory synapses, short term plasticity. We also found that this calcium signaling decreases basal transmission and short term plasticity of hippocampal excitatory synapses. Altogether, these results suggest that fine tuning of various astroglial properties are involved to ensure proper synaptic function.

Publications

2Chever O., Dossi E. et Rouach N., « Contrôle astroglial de la synchronisation neuronale : “mind the GAP !” », Médecine/sciences, vol. 32, n^o 10, 2016, p. 820-822, DOI : 10.1051/medsci/20163210010.

Depauw A., Dossi E., Kumar N., Fiorini-Debuisschert C., Huberfeld G., Ha-Thi M.-H., Rouach N. et Leray I., « A highly selective potassium sensor for the detection of potassium in living tissues », Chemistry. A European Journal, vol. 22, n^o 42, 2016, p. 14902-14911, DOI : 10.1002/chem.201602209.

Lee C.-Y., Dallérac G., Ezan P., Anderova M. et Rouach N., « Glucose tightly controls morphological and functional properties of astrocytes », Frontiers in Aging Neuroscience, vol. 8, n^o 82, 2016, DOI : 10.3389/fnagi.2016.00082.

Dallérac G. et Rouach N., « Astrocytes as new targets to improve cognitive functions », Progress in Neurobiology, 2016, DOI : 10.1016/j.pneurobio.2016.01.003.

Boillot M., Lee C.-Y., Allene C., Leguern E., Baulac S. et Rouach N., « LGI1 acts presynaptically to regulate excitatory synaptic transmission during early postnatal development », Scientific Reports, vol. 6, n^o 21769, 2016, DOI : 10.1038/srep21769.

Chever O., Dossi E., Pannasch U., Derangeon M. et Rouach N., « Astroglial networks promote neuronal coordination », Science Signaling, vol. 9, n^o 410, 2016, ra6, DOI : 10.1126/scisignal.aad3066.

Boulay A.-C., Cisternino S. et Cohen-Salmon M., « Immunoregulation at the gliovascular unit in the healthy brain: A focus on Connexin 43 », Brain, Behavior, and Immunity, vol. 56, 2016, p. 1-9, DOI : 10.1016/j.bbi.2015.11.017.

Olsen M.L., Khakh B.S., Skatchkov S.N., Zhou M., Lee C.J. et Rouach N., « New insights on astrocyte ion channels: Critical for homeostasis and neuron-glia signaling », The Journal of Neuroscience, vol. 35, n^o 41, 2015, p. 13827-13835, DOI : 10.1523/JNEUROSCI.2603-15.2015.

Cheung G., Sibille J., Zapata J. et Rouach N., « Activity-dependent plasticity of astroglial potassium and glutamate clearance », Neural Plasticity, vol. 2015, 109106, 2015, DOI : 10.1155/2015/109106.

Reynaud K., Schuss Z., Rouach N. et Holcman D., « Why so many sperm cells? », Communicative and Integrative Biology, vol. 8, n^o 3, 2015, e1017156.

Ghézali G., Dallérac G. et Rouach N., « Perisynaptic astroglial processes: Dynamic processors of neuronal information », Brain Structure & Function, vol. 221, n^o 5, 2015, DOI : 10.1007/s00429-015-1070-3.

Sibille J., Zapata J., Teillon J. et Rouach N., « Astroglial calcium signaling displays short-term plasticity and adjusts synaptic efficacy », Frontiers in Cellular Neuroscience, vol. 9, n^o 189, 2015, DOI : 10.3389/fncel.2015.00189.

Dao Duc K., Lee C.Y., Parutto P., Cohen D., Segal M., Rouach N. et Holcman D., « Bursting reverberation as a multiscale neuronal network process driven by synaptic depression-facilitation », PloS One, vol. 10, n^o 5, 2015, e0124694, DOI : 10.1371/journal.pone.0124694.

Sibille J., Dao Duc K., Holcman D. et Rouach N., « The neuroglial potassium cycle during neurotransmission: Role of Kir4.1 Channels », PLoS computational biology, vol. 11, n^o 3, 2015, e1004137, DOI : 10.1371/journal.pcbi.1004137.

Abudara V., Roux L., Dallérac G., Matias I., Dulong J., Mothet J.P., Rouach N. et Giaume C., « Activated microglia impairs neuroglial interaction by opening Cx43 hemichannels in hippocampal astrocytes », Glia, vol. 63, n^o 5, 2015, p. 795-811, DOI : 10.1002/glia.22785.

Seidel J.L., Faideau M., Aiba I., Pannasch U., Escartin C., Rouach N., Bonvento G. et Shuttleworth C.W., « Ciliary neurotrophic factor (CNTF) activation of astrocytes decreases spreading depolarization susceptibility and increases potassium clearance », Glia, vol. 63, n^o 1, p. 91-103, 2015, DOI : 10.1002/glia.22735.

Boulay A.-C., Mazeraud A., Cisternino S., Saubaméa B., Mailly P., Jourdren L., Blugeon C., Mignon V., Smirnova M., Cavallo A., Ezan P., Avé P., Dingli F., Loew D., Vieira P., Chrétien F. et Cohen-Salmon M., « Immune quiescence of the brain is set by astroglial connexin 43 », The Journal of Neuroscience, vol. 35, n^o 10, 2015, p. 4427-4439, DOI : 10.1523/JNEUROSCI.2575-14.2015.

Boulay A.-C., Saubaméa B., Cisternino S., Mignon V., Mazeraud A., Jourdren L., Blugeon C. et Cohen-Salmon M., « The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels », Frontiers in Cellular Neuroscience, vol. 9, n^o 9, 2015, DOI : 10.3389/fncel.2015.00009.

Boulay A.-C., Saubaméa B., Declèves X. et Cohen-Salmon M., « Purification of mouse brain vessels », Journal of Visualized Experiments: JoVE, n^o 105, 2015, e53208, DOI : 10.3791/53208.