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Séminaire - Giorgio Carmignoto Astrocytes at the centre of a brain of neurones

Abstract :

A full understanding the role of astrocytes in the neuronal network would provide new insights into brain function and dysfunction. It also represents a formidable challenge for  modern neurobiological research in both conceptual and technological terms. We recently focused our reseach on epilepsy, and more specifically, on the early cellular events that lead to the initiation of a focal seizure, govern seizure propagation and dictate seizure cessation. Identification and characterization of these early events is fundamental for developing new therapeutic approaches. As revealed by a number of studies, gliotransmitters released from astrocytes differently modulate synaptic transmission and favor neuronal shynchrony.

In a brain network prone to seizures, glutamate released from early activated astrocytes can lower seizure threshold by enhancing synchronous discharges in pyramidal neurons (Gomez et al., 2010). It is unclear, however, whether astrocytic glutamate acting on GABAergic inhibitory interneurons can have  a different impact on network activities. GABAergic transmission opposes seizure generation and propagation, but in certain conditions it may favor epileptiform activities by synchronizing large neuronal populations or by becoming excitatory.
Also noteworthy is that beside glutamate, astrocytes release GABA and adenosine that can have different effects on seizure activity. We investigated whether the reciprocal signalling occurring between astrocytes and excitatory glutamatergic neurons may be extended to inhibitory GABAergic interneurons. 
Our final goal is understanding whether astrocyte signalling may have a pro- or an anti-convulsant action taking into account the hypothesis that the action of gliotrasmission on ictogenesis may ultimately be context-dependent.

Selected publications

Araque A., Carmignoto G., HaydonP.G., Oliet S.H.R., Robitaille R., Volterra A. (2014) Gliotransmitters Travel in Time and Space. Neuron (in press)

Cammarota M., Losi G., Chiavegato A., Zonta M. and Carmignoto G. (2013) Fast spiking interneuron control of seizure propagation in a cortical slice model of focal epilepsy.The Journal of Physiology 591, 807-822.

Crunelli V. and Carmignoto G. (2013) New vistas on astroglia in convulsive and non-convulsive epilepsy highlight novel astrocytic target for treatment. The Journal of Physiology  591, 775-785.

Gómez-Gonzalo M., Losi G, Chiavegato A., Zonta M., Cammarota M.,   Brondi M., Vetri F., Uva L., Pozzan T., de Curtis M., Ratto G.M., Carmignoto G. (2010). An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold. PLoS Biology  8, 4, 1-19.

Haydon P.G. and Carmignoto G. (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol. Rev.  86, 1009-1031.

Fellin T., Pascual O., Gobbo S., Pozzan T., HaydonP.G. and Carmignoto G. (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43, 729-743.

Scientific focus :

Dr Giorgio Carmignoto is group leader at the Institute of Neuroscience which belongs to the National Research Council (CNR), the main public research organization in Italy. He is also associated with the Department of Experimental Biomedical Science of the University of Padova. The central theme of his research is the specific signalling between neurons and astrocytes investigated by laser-scanning microscope living cell imaging and patch-clamp recording techniques. Among obtained results are the first evidence for the ability of astrocytes i) to be activated by neurotransmitter synaptic release in slice preparations ; ii) to work as principal mediators of neurovascular coupling; iii) to generate neuronal synchrony by acting on extrasynaptic NMDA receptors. His research is now focused on the role of astrocytes in epilepsy.

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