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24 publication(s) depuis Septembre 2004:

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19/10/2014 | Philos Trans R Soc Lond B Biol Sci   IF 6.1
Dissecting tripartite synapses with STED microscopy.
Panatier A, Arizono M, Nagerl UV

The concept of the tripartite synapse reflects the important role that astrocytic processes are thought to play in the function and regulation of neuronal synapses in the mammalian nervous system. However, many basic aspects regarding the dynamic interplay between pre- and postsynaptic neuronal structures and their astrocytic partners remain to be explored. A major experimental hurdle has been the small physical size of the relevant glial and synaptic structures, leaving them largely out of reach for conventional light microscopic approaches such as confocal and two-photon microscopy. Hence, most of what we know about the organization of the tripartite synapse is based on electron microscopy, which does not lend itself to investigating dynamic events and which cannot be carried out in parallel with functional assays. The development and application of superresolution microscopy for neuron-glia research is opening up exciting experimental opportunities in this regard. In this paper, we provide a basic explanation of the theory and operation of stimulated emission depletion (STED) microscopy, outlining the potential of this recent superresolution imaging modality for advancing our understanding of the morpho-functional interactions between astrocytes and neurons that regulate synaptic physiology.

2013 | J Med Chem   IF 6.1
Structural, Kinetic, and Pharmacodynamic Mechanisms of d-Amino Acid Oxidase Inhibition by Small Molecules
Hopkins SC, Heffernan MLR, Saraswat LD, Bowen CA, Melnick L, Hardy LW, Orsini MA, Allen MS, Koch P, Spear KL, Foglesong RJ , Soukri M, Chytil M, Fang QK, Jones SW, Varney MA, Panatier A, Oliet SHR, Pollegioni L, Piubelli L, Molla G, Nardini M, Large TH

We characterized the mechanism and pharmacodynamics of five structurally distinct inhibitors of d-amino acid oxidase. All inhibitors bound the oxidized form of human enzyme with affinity slightly higher than that of benzoate (Kd ≈ 2-4 μM). Stopped-flow experiments showed that pyrrole-based inhibitors possessed high affinity (Kd ≈ 100-200 nM) and slow release kinetics (k < 0.01 s(-1)) in the presence of substrate, while inhibitors with pendent aromatic groups altered conformations of the active site lid, as evidenced by X-ray crystallography, and showed slower kinetics of association. Rigid bioisosteres of benzoic acid induced a closed-lid conformation, had slower release in the presence of substrate, and were more potent than benzoate. Steady-state d-serine concentrations were described in a PK/PD model, and competition for d-serine sites on NMDA receptors was demonstrated in vivo. DAAO inhibition increased the spatiotemporal influence of glial-derived d-serine, suggesting localized effects on neuronal circuits where DAAO can exert a neuromodulatory role

11/12/2012 | Dev Cell   IF 9.2
The soothing touch: microglial contact influences neuronal excitability.
Panatier A, Robitaille R

Resting microglial cells in the brain scan their environment with their processes, primed to react to injury and disease. In this issue of Developmental Cell, Li and colleagues (2012) report that resting microglia also react to physiological neuronal activity, sending their processes toward highly active neurons to regulate their excitability.

06/2012 | Med Sci (Paris)   IF 0.4
[Astrocyte, a key partner of neurons during basal synaptic transmission].
Panatier A, Robitaille R


02/09/2011 | Cell   IF 36.2
Astrocytes are endogenous regulators of Basal transmission at central synapses.
Panatier A, Vallee J, Haber M, Murai KK, Lacaille JC, Robitaille R

Basal synaptic transmission involves the release of neurotransmitters at individual synapses in response to a single action potential. Recent discoveries show that astrocytes modulate the activity of neuronal networks upon sustained and intense synaptic activity. However, their ability to regulate basal synaptic transmission remains ill defined and controversial. Here, we show that astrocytes in the hippocampal CA1 region detect synaptic activity induced by single-synaptic stimulation. Astrocyte activation occurs at functional compartments found along astrocytic processes and involves metabotropic glutamate subtype 5 receptors. In response, astrocytes increase basal synaptic transmission, as revealed by the blockade of their activity with a Ca(2+) chelator. Astrocytic modulation of basal synaptic transmission is mediated by the release of purines and the activation of presynaptic A(2A) receptors by adenosine. Our work uncovers an essential role for astrocytes in the regulation of elementary synaptic communication and provides insight into fundamental aspects of brain function.

The hypothalamo-neurohypophysial system is comprised of magnocellular neurones that synthesise the neuropeptides oxytocin or vasopressin. As neurohormones, these peptides intervene in the regulation of vital functions such as parturition, lactation, osmotic and cardiovascular regulation. The release of these peptides in the general circulation depends on the electrical activity of their parent neurones, which in turn is regulated by the activity of their afferent inputs conveying distinct information. Thus, in view of the diversity of information governing the activity of magnocellular neurones, it is crucial that the system adapts the appropriate release of oxytocin and vasopressin upon physiological demand. Until recently, it was considered that only neurones could provide such adaptation and regulation. However, a third partner of the synapse, the astrocyte, has been shown to provide further control. Astrocytic processes are in proximity of the magnocellular neurones and their synapses, well positioned to detect and modulate synaptic signals. For instance, astrocytes detect a synaptic signal owing to their diverse neurotransmitter/neuropeptide receptors. In addition, they release a variety of neuroactive substances (i.e. gliotransmitters), which in turn modulate synaptic activity. An important gliotransmitter is the amino acid, d-serine, which, together with glutamate, activates NMDA receptors. Once activated, NMDA receptors govern the weight of individual inputs on magnocellular neurones and thus the impact of distinct types of information on neuronal activity. As reviewed here, numerous observations show that astrocytes must be considered as key elements in the functioning of the hypothalamo-neurohypophysial system.

2008 | Prog Brain Res   IF 3
Neuron-glia interactions in the rat supraoptic nucleus.
Oliet SH, Panatier A, Piet R, Mothet JP, Poulain DA, Theodosis DT

The adult hypothalamo-neurohypophysial system undergoes a striking activity-dependent morphological remodelling that modifies the glial enwrapping of its magnocellular neurons. Although the functional consequences of such remodelling remain hypothetical, recent evidence has provided new insights into the repercussions of glial environment modifications on the physiology of magnocellular neurosecretory cells at the synaptic level. These studies have revealed that the reduced astrocytic coverage of magnocellular neurons occurring in the SON affects various functions in which astrocytes play key roles. These functions include uptake of neurotransmitters such as glutamate, restricting diffusion of neuroactive substances within the extracellular space and release of informative molecules known as gliotransmitters that act on neighbouring neurons to modulate synaptic transmission and excitability. Overall, our observations indicate that the neuron-glial anatomical reorganization leads to modifications of glutamatergic transmission that might be important for the physiology of the hypothalamo-neurohypophysial system.

08/2007 | PLoS Biol   IF 8.4
Spatial learning depends on both the addition and removal of new hippocampal neurons.
Dupret D, Fabre A, Dobrossy MD, Panatier A, Rodriguez JJ, Lamarque S, Lemaire V, Oliet SH, Piazza PV, Abrous DN

The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons.

15/06/2006 | J Physiol   IF 5
Activity-dependent synaptic plasticity in the supraoptic nucleus of the rat hypothalamus.
Panatier A, Gentles SJ, Bourque CW, Oliet SH

Activity-dependent long-term synaptic changes were investigated at glutamatergic synapses in the supraoptic nucleus (SON) of the rat hypothalamus. In acute hypothalamic slices, high frequency stimulation (HFS) of afferent fibres caused long-term potentiation (LTP) of the amplitude of AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) recorded with the whole-cell patch-clamp technique. LTP was also obtained in response to membrane depolarization paired with mild afferent stimulation. On the other hand, stimulating the inputs at 5 Hz for 3 min at resting membrane potential caused long-term depression (LTD) of excitatory transmission in the SON. These forms of synaptic plasticity required the activation of NMDA receptors since they were abolished in the presence of D-AP5 or ifenprodil, two selective blockers of these receptors. Analysis of paired-pulse facilitation and trial-to-trial variability indicated that LTP and LTD were not associated with changes in the probability of transmitter release, thereby suggesting that the locus of expression of these phenomena was postsynaptic. Using sharp microelectrode recordings in a hypothalamic explant preparation, we found that HFS also generates LTP at functionally defined glutamatergic synapses formed between the organum vasculosum lamina terminalis and SON neurons. Taken together, our findings indicate that glutamatergic synapses in the SON exhibit activity-dependent long-term synaptic changes similar to those prevailing in other brain areas. Such forms of plasticity could play an important role in the context of physiological responses, like dehydration or lactation, where the activity of presynaptic glutamatergic neurons is strongly increased.

19/05/2006 | Cell   IF 36.2
Glia-derived D-serine controls NMDA receptor activity and synaptic memory.
Panatier A, Theodosis DT, Mothet JP, Touquet B, Pollegioni L, Poulain DA, Oliet SH

The NMDA receptor is a key player in excitatory transmission and synaptic plasticity in the central nervous system. Its activation requires the binding of both glutamate and a co-agonist like D-serine to its glycine site. As D-serine is released exclusively by astrocytes, we studied the physiological impact of the glial environment on NMDA receptor-dependent activity and plasticity. To this end, we took advantage of the changing astrocytic ensheathing of neurons occurring in the supraoptic nucleus during lactation. We provide direct evidence that in this hypothalamic structure the endogenous co-agonist of NMDA receptors is D-serine and not glycine. Consequently, the degree of astrocytic coverage of neurons governs the level of glycine site occupancy on the NMDA receptor, thereby affecting their availability for activation and thus the activity dependence of long-term synaptic changes. Such a contribution of astrocytes to synaptic metaplasticity fuels the emerging concept that astrocytes are dynamic partners of brain signaling.