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Stéphane OLIET


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PhD, McGill University (1994)
Posdoc, UCSF (1994-1997) HFSP fellow
CR1 CNRS, Inserm U378(2001)
HDR, Université Bordeaux 2 (2003)
DR1 CNRS, Neurocentre Magendie Inserm (2009)

Expertise: Astrocyte, gliotransmitters, plasticity, synapse, NMDA receptors

99 publication(s) depuis Juillet 1991:

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* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en

21/09/2020 | Neuron   IF 14.4
LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia.
Henneberger C*, Bard L*, Panatier A*, Reynolds JP, Kopach O, Medvedev NI, Minge D, Herde MK, Anders S, Kraev I, Heller JP, Rama S, Zheng K, Jensen TP, Sanchez-Romero I, Jackson CJ, Janovjak H, Ottersen OP, Nagelhus EA, Oliet SHR, Stewart MG*, Nagerl V*, Rusakov DA*

Extrasynaptic actions of glutamate are limited by high-affinity transporters expressed by perisynaptic astroglial processes (PAPs): this helps maintain point-to-point transmission in excitatory circuits. Memory formation in the brain is associated with synaptic remodeling, but how this affects PAPs and therefore extrasynaptic glutamate actions is poorly understood. Here, we used advanced imaging methods, in situ and in

18/05/2020 | Nat Commun   IF 12.1
Author Correction: Structural basis of astrocytic Ca(2+) signals at tripartite synapses.
Arizono M, Inavalli VVGK, Panatier A, Pfeiffer T, Angibaud J, Levet F, Veer MJTT, Stobart J, Bellocchio L, Mikoshiba K, Marsicano G, Weber B, Oliet SHR, Nagerl UV

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

20/04/2020 | Nat Commun   IF 12.1
Structural basis of astrocytic Ca(2+) signals at tripartite synapses.
Arizono M, Inavalli VVGK, Panatier A, Pfeiffer T, Angibaud J, Levet F, Ter Veer MJT, Stobart J, Bellocchio L, Mikoshiba K, Marsicano G, Weber B, Oliet SHR, Nagerl UV

Astrocytic Ca(2+) signals can be fast and local, supporting the idea that astrocytes have the ability to regulate single synapses. However, the anatomical basis of such specific signaling remains unclear, owing to difficulties in resolving the spongiform domain of astrocytes where most tripartite synapses are located. Using 3D-STED microscopy in living organotypic brain slices, we imaged the spongiform domain of astrocytes and observed a reticular meshwork of nodes and shafts that often formed loop-like structures. These anatomical features were also observed in acute hippocampal slices and in barrel cortex in vivo. The majority of dendritic spines were contacted by nodes and their sizes were correlated. FRAP experiments and Ca(2+) imaging showed that nodes were biochemical compartments and Ca(2+) microdomains. Mapping astrocytic Ca(2+) signals onto STED images of nodes and dendritic spines showed they were associated with individual synapses. Here, we report on the nanoscale organization of astrocytes, identifying nodes as a functional astrocytic component of tripartite synapses that may enable synapse-specific communication between neurons and astrocytes.

03/03/2020 | Cell Metab   IF 21.6
Impairment of Glycolysis-Derived l-Serine Production in Astrocytes Contributes to Cognitive Deficits in Alzheimer's Disease.
Le Douce J, Maugard M, Veran J, Matos M, Jego P, Vigneron PA, Faivre E, Toussay X, Vandenberghe M, Balbastre Y, Piquet J, Guiot E, Tran NT, Taverna M, Marinesco S, Koyanagi A, Furuya S, Gaudin-Guerif M, Goutal S, Ghettas A, Pruvost A, Bemelmans AP, Gaillard MC, Cambon K, Stimmer L, Sazdovitch V, Duyckaerts C, Knott G, Herard AS, Delzescaux T, Hantraye P, Brouillet E, Cauli B, Oliet SHR, Panatier A, Bonvento G

Alteration of brain aerobic glycolysis is often observed early in the course of Alzheimer's disease (AD). Whether and how such metabolic dysregulation contributes to both synaptic plasticity and behavioral deficits in AD is not known. Here, we show that the astrocytic l-serine biosynthesis pathway, which branches from glycolysis, is impaired in young AD mice and in AD patients. l-serine is the precursor of d-serine, a co-agonist of synaptic NMDA receptors (NMDARs) required for synaptic plasticity. Accordingly, AD mice display a lower occupancy of the NMDAR co-agonist site as well as synaptic and behavioral deficits. Similar deficits are observed following inactivation of the l-serine synthetic pathway in hippocampal astrocytes, supporting the key role of astrocytic l-serine. Supplementation with l-serine in the diet prevents both synaptic and behavioral deficits in AD mice. Our findings reveal that astrocytic glycolysis controls cognitive functions and suggest oral l-serine as a ready-to-use therapy for AD.

25/06/2019 | Cell Rep   IF 7.8
Aquaporin-4 Surface Trafficking Regulates Astrocytic Process Motility and Synaptic Activity in Health and Autoimmune Disease.
Ciappelloni S, Bouchet D, Dubourdieu N, Boue-Grabot E, Kellermayer B, Manso C, Marignier R, Oliet SHR, Tourdias T, Groc L

Astrocytes constantly adapt their ramified morphology in order to support brain cell assemblies. Such plasticity is partly mediated by ion and water fluxes, which rely on the water channel aquaporin-4 (AQP4). The mechanism by which this channel locally contributes to process dynamics has remained elusive. Using a combination of single-molecule and calcium imaging approaches, we here investigated in hippocampal astrocytes the dynamic distribution of the AQP4 isoforms M1 and M23. Surface AQP4-M1 formed small aggregates that contrast with the large AQP4-M23 clusters that are enriched near glutamatergic synapses. Strikingly, stabilizing surface AQP4-M23 tuned the motility of astrocyte processes and favors glutamate synapse activity. Furthermore, human autoantibodies directed against AQP4 from neuromyelitis optica (NMO) patients impaired AQP4-M23 dynamic distribution and, consequently, astrocyte process and synaptic activity. Collectively, it emerges that the membrane dynamics of AQP4 isoform regulate brain cell assemblies in health and autoimmune brain disease targeting AQP4.

20/12/2018 | j neuroinflammation   IF 5.2
Sequential alteration of microglia and astrocytes in the rat thalamus following spinal nerve ligation.
Blaszczyk L, Maitre M, Leste-Lasserre T, Clark S, Cota D, Oliet SHR, Fenelon VS

BACKGROUND: Spinal reactive astrocytes and microglia are known to participate to the initiation and maintenance of neuropathic pain. However, whether reactive astrocytes and microglia in thalamic nuclei that process sensory-discriminative aspects of pain play a role in pain behavior remains poorly investigated. Therefore, the present study evaluated whether the presence of reactive glia (hypertrophy, increased number and upregulation of glial markers) in the ventral posterolateral thalamic nucleus (VPL) correlates with pain symptoms, 14 and 28 days after unilateral L5/L6 spinal nerve ligation (SNL) in rats. METHODS: Mechanical allodynia and hyperalgesia (von Frey filament stimulation) as well as ambulatory pain (dynamic weight bearing apparatus) were assessed. Levels of nine glial transcripts were determined by quantitative real-time PCR on laser microdissected thalamic nuclei, and levels of proteins were assessed by Western blot. We also studied by immunohistofluorescence the expression of glial markers that label processes (GFAP for astrocytes and iba-1 for microglia) and cell body (S100beta for astrocytes and iba-1 for microglia) and quantified the immunostained surface and the number of astrocytes and microglia (conventional counts and optical dissector method of stereological counting). RESULTS: Differential, time-dependent responses were observed concerning microglia and astrocytes. Specifically, at day 14, iba-1 immunostained area and number of iba-1 immunopositive cells were decreased in the VPL of SNL as compared to naive rats. By contrast, at day 28, GFAP-immunostained area was increased in the VPL of SNL as compared to naive rats while number of GFAP/S100beta immunopositive cells remained unchanged. Using quantitative real-time PCR of laser microdissected VPL, we found a sequential increase in mRNA expression of cathepsin S (day 14), fractalkine (day 28), and fractalkine receptor (day 14), three well-known markers of microglial reactivity. Using Western blot, we confirmed an increase in protein expression of fractalkine receptor at day 14. CONCLUSIONS: Our results demonstrate a sequential alteration of microglia and astrocytes in the thalamus of animals with lesioned peripheral nerves. Furthermore, our data report unprecedented concomitant molecular signs of microglial activation and morphological signs of microglial decline in the thalamus of these animals.

16/10/2018 | Acta Neuropathol Commun   IF 5.4
Modulation of astrocyte reactivity improves functional deficits in mouse models of Alzheimer's disease.
Ceyzeriat K, Ben Haim L, Denizot A, Pommier D, Matos M, Guillemaud O, Palomares MA, Abjean L, Petit F, Gipchtein P, Gaillard MC, Guillermier M, Bernier S, Gaudin M, Auregan G, Josephine C, Dechamps N, Veran J, Langlais V, Cambon K, Bemelmans AP, Baijer J, Bonvento G, Dhenain M, Deleuze JF, Oliet SHR, Brouillet E, Hantraye P, Carrillo-de Sauvage MA, Olaso R, Panatier A, Escartin C

Astrocyte reactivity and neuroinflammation are hallmarks of CNS pathological conditions such as Alzheimer's disease. However, the specific role of reactive astrocytes is still debated. This controversy may stem from the fact that most strategies used to modulate astrocyte reactivity and explore its contribution to disease outcomes have only limited specificity. Moreover, reactive astrocytes are now emerging as heterogeneous cells and all types of astrocyte reactivity may not be controlled efficiently by such strategies.Here, we used cell type-specific approaches in vivo and identified the JAK2-STAT3 pathway, as necessary and sufficient for the induction and maintenance of astrocyte reactivity. Modulation of this cascade by viral gene transfer in mouse astrocytes efficiently controlled several morphological and molecular features of reactivity. Inhibition of this pathway in mouse models of Alzheimer's disease improved three key pathological hallmarks by reducing amyloid deposition, improving spatial learning and restoring synaptic deficits.In conclusion, the JAK2-STAT3 cascade operates as a master regulator of astrocyte reactivity in vivo. Its inhibition offers new therapeutic opportunities for Alzheimer's disease.

06/06/2018 | Neuron   IF 14.3
Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory.
Robin LM*, Cruz J*, Oliveira da Cruz JF, Langlais VC, Martin-Fernandez M, Metna-Laurent M, Busquets-Garcia A, Bellocchio L, Soria-Gomez E, Papouin T, Varilh M, Sherwood MW, Belluomo I, Balcells G, Matias I, Bosier B, Drago F, Van Eeckhaut A, Smolders I, Georges F, Araque A, Panatier A, Oliet SHR*, Marsicano G*

Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB1 receptors from astroglial cells (GFAP-CB1-KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB1 receptors increased intracellular astroglial Ca(2+) levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB1-KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB1-KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs.

02/03/2018 | Sci Rep   IF 4.1
Metabolic Reprogramming in Amyotrophic Lateral Sclerosis.
Szelechowski M, Amoedo N, Obre E, Leger C, Allard L, Bonneu M, Claverol S, Lacombe D, Oliet S, Chevallier S, Le Masson G, Rossignol R

Mitochondrial dysfunction in the spinal cord is a hallmark of amyotrophic lateral sclerosis (ALS), but the neurometabolic alterations during early stages of the disease remain unknown. Here, we investigated the bioenergetic and proteomic changes in ALS mouse motor neurons and patients' skin fibroblasts. We first observed that SODG93A mice presymptomatic motor neurons display alterations in the coupling efficiency of oxidative phosphorylation, along with fragmentation of the mitochondrial network. The proteome of presymptomatic ALS mice motor neurons also revealed a peculiar metabolic signature with upregulation of most energy-transducing enzymes, including the fatty acid oxidation (FAO) and the ketogenic components HADHA and ACAT2, respectively. Accordingly, FAO inhibition altered cell viability specifically in ALS mice motor neurons, while uncoupling protein 2 (UCP2) inhibition recovered cellular ATP levels and mitochondrial network morphology. These findings suggest a novel hypothesis of ALS bioenergetics linking FAO and UCP2. Lastly, we provide a unique set of data comparing the molecular alterations found in human ALS patients' skin fibroblasts and SODG93A mouse motor neurons, revealing conserved changes in protein translation, folding and assembly, tRNA aminoacylation and cell adhesion processes.

30/01/2018 | Neuroimage   IF 5.4
Deciphering the microstructure of hippocampal subfields with in vivo DTI and NODDI: Applications to experimental multiple sclerosis.
Crombe A, Planche V, Raffard G, Bourel J, Dubourdieu N, Panatier A, Fukutomi H, Dousset V, Oliet S, Hiba B, Tourdias T

The hippocampus contains distinct populations of neurons organized into separate anatomical subfields and layers with differential vulnerability to pathological mechanisms. The ability of in vivo neuroimaging to pinpoint regional vulnerability is especially important for better understanding of hippocampal pathology at the early stage of neurodegenerative disorders and for monitoring future therapeutic strategies. This is the case for instance in multiple sclerosis whose neurodegenerative component can affect the hippocampus from the early stage. We challenged the capacity of two models, i.e. the classical diffusion tensor imaging (DTI) model and the neurite orientation dispersion and density imaging (NODDI) model, to compute quantitative diffusion MRI that could capture microstructural alterations in the individual hippocampal layers of experimental-autoimmune encephalomyelitis (EAE) mice, the animal model of multiple sclerosis. To achieve this, the hippocampal anatomy of a healthy mouse brain was first explored ex vivo with high resolution DTI and NODDI. Then, 18 EAE mice and 18 control mice were explored 20 days after immunization with in vivo diffusion MRI prior to sacrifice for the histological quantification of neurites and glial markers in each hippocampal layer. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) maps were computed from the DTI model while the orientation dispersion index (ODI), the neurite density index (NDI) and the volume fraction of isotropic diffusivity (isoVF) maps were computed from the NODDI model. We first showed in control mice that color-coded FA and ODI maps can delineate three main hippocampal layers. The quantification of FA, AD, RD, MD, ODI, NDI and isoVF presented differences within these 3 layers, especially within the molecular layer of the dentate gyrus which displayed a specific signature based on a combination of AD (or MD), ODI and NDI. Then, the comparison between EAE and control mice showed a decrease of AD (p=0.036) and of MD (p=0.033) selectively within the molecular layer of EAE mice while NODDI indices did not present any difference between EAE and control mice in any layer. Histological analyses confirmed the differential vulnerability of the molecular layer of EAE mice that exhibited decreased dendritic length and decreased dendritic complexity together with activated microglia. Dendritic length and intersections within the molecular layer were independent contributors to the observed decrease of AD (R(2)=0.37 and R(2)=0.40, p<0.0001) and MD (R(2)=0.41 and R(2)=0.42, p<0.0001). We therefore identified that NODDI maps can help to highlight the internal microanatomy of the hippocampus but NODDI still presents limitations in grey matter as it failed to capture selective dendritic alterations occurring at early stages of a neurodegenerative disease such as multiple sclerosis, whereas DTI maps were significantly altered.