NeuroGLIA Consortium: neuron-astroglia in brain function and dysfunction

Brief description and aims of work

My group focuses on the molecular, cellular and network mechanisms that underlie the expression of physiological and pathological rhythms/oscillations in thalamocortical circuits, with special relevance to sleep and epilepsy. Within this aim, we have been interested in astroglia-neuron interactions in thalamus since 1999, and in collaboration with Dr R.H. Parri (Aston University, Birmingham, UK) we were the first to report in 2001 the existence of spontaneous astrocytic signalling to neuron in the absence of synaptic transmission, and their mediation by neuronal NMDA receptors. We use a multi-disciplinary anatomical, computational, electrophysiological and imaging approach, and combine in vitro work in brain slices with analysis of naturally waking and sleeping, freely moving animals.

In particular, our objectives are:

• To characterize the mechanism that underlies the slow inward and outward currents that are selectively elicited in neurones by the spontaneous astrocytic release of glutamate and GABA, respectively.
• To define the (patho)physiological role of ambient glutamate in astroglia-neuron interactions.
• To identify the precise contribution of astroglia to the generation and spread of absence seizures, using both inbred genetic models (GAERS, stargazer, tottering mice) and a pharmacological model (i.e., gamma-hydroxybutyric acid) of absence seizures.

Implications of our research

The emerging view see astrocytes as playing key roles in brain function. Indeed, we believe that both physiological and pathological brain oscillations cannot be fully understood without gaining full knowledge not only of neuronal synchronization but also of astroglia-neuron interactions.

Selected references

Original articles

1. Parri R, Crunelli V (2007) Astrocytes target presynaptic NMDA receptors to give synapses a boost. Nat. Neurosci. 10:271-3.
2. Gervasi N, Monnier Z, Vincent P, Paupardin-Tritsch D, Hughes SW, Crunelli V, Leresche N (2003) Pathway-specific action of gamma-hydroxybutyric acid in sensory thalamus and its relevance to absence seizures. J. Neurosci. 23:11469-78.
3. Parri R, Crunelli V (2003) An astrocyte bridge from synapse to blood flow. Nat. Neurosci. 6:5-6.
4. Parri HR, Crunelli V (2003) The role of Ca²⁺ in the generation of spontaneous astrocytic Ca²⁺ oscillations. Neuroscience 120:979-92.
5. Parri HR, Gould TM, Crunelli V (2001) Spontaneous astrocytic Ca²⁺ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat. Neurosci. 4:803-12.
6. Parri HR, Crunelli V (2001) Pacemaker calcium oscillations in thalamic astrocytes in situ. Neuroreport 12:3897-900.

Reviews

1. Crunelli V, Emri Z, Leresche N (2006) Unravelling the brain targets of gamma-hydroxybutyric acid. Curr. Opin. Pharmacol. 6:44-52.
2. Parri HR, Crunelli V (2002) Astrocytes, spontaneity, and the developing thalamus. J. Physiol. (Paris) 96:221-30.
3. Crunelli V, Blethyn KL, Cope DW, Hughes SW, Parri HR, Turner JP, Tòth TI, Williams SR (2002) Novel neuronal and astrocytic mechanisms in thalamocortical loop dynamics. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 357:1675-93.
4. Crunelli V, Leresche N (2002) Childhood Absence Epilepsy: genes, channels, neurons and networks. Nature Rev. Neurosci. 3:371-382.

Past and present collaborations

• Rheinallt H. Parri · Molecular Biosciences, School of Life and Health Sciences, Aston University, Birmingham, UK
• John G. Parnavelas · Department of Anatomy & Developmental Biology, University College London, London, UK
• Stuart W. Hughes · Neuroscience Group,School of Bioscience, Cardiff University, Cardiff, UK
• Nathalie Leresche · Equipe "Réseaux de Neurones et Rythmes Physiopathologiques", UMR 7102 CNRS-UPMC, Université P & M Curie, Paris, France
• Klaus Willecke · Institut für Genetik, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany
• Hee-Sup Shin · Center for Neural Science, Korea Institute of Science and Technology, Seoul, Republic of Korea