Neurocentre Magendie



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PhD Neurosciences et Neuropharmacologie (1998)
PostDoc Brandeis University, Boston(1992-1993)
CR1 INSERM (1994-2003)
Prof Université CHU Bordeaux (2003)
Invited Prof at Columbia University (2008-2009)

18 publication(s) depuis Février 2000:

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

10/11/2014 | Nat Neurosci   IF 16.7
Dendritic channelopathies contribute to neocortical and sensory hyperexcitability in Fmr1 mice.
Zhang Y*, Bonnan A*, Bony G*, Ferezou I, Pietropaolo S, Ginger M, Sans N, Rossier J, Oostra B, Lemasson G, Frick A

Hypersensitivity in response to sensory stimuli and neocortical hyperexcitability are prominent features of Fragile X Syndrome (FXS) and autism spectrum disorders, but little is known about the dendritic mechanisms underlying these phenomena. We found that the primary somatosensory neocortex (S1) was hyperexcited in response to tactile sensory stimulation in Fmr1-/y mice. This correlated with neuronal and dendritic hyperexcitability of S1 pyramidal neurons, which affect all major aspects of neuronal computation, from the integration of synaptic input to the generation of action potential output. Using dendritic electrophysiological recordings, calcium imaging, pharmacology, biochemistry and a computer model, we found that this defect was, at least in part, attributable to the reduction and dysfunction of dendritic h- and BKCa channels. We pharmacologically rescued several core hyperexcitability phenomena by targeting BKCa channels. Our results provide strong evidence pointing to the utility of BKCa channel openers for the treatment of the sensory hypersensitivity aspects of FXS.

20/08/2014 | Neuron   IF 14
A Computational Model of Motor Neuron Degeneration
Le masson G, przedborski, Serge, Abbott, LF

To explore the link between bioenergetics and mo- tor neuron degeneration, we used a computational model in which detailed morphology and ion conductance are paired with intracellular ATP pro- duction and consumption. We found that reduced ATP availability increases the metabolic cost of a single action potential and disrupts K+/Na+ homeo- stasis, resulting in a chronic depolarization. The magnitude of the ATP shortage at which this ionic instability occurs depends on the morphology and intrinsic conductance characteristic of the neuron. If ATP shortage is confined to the distal part of the axon, the ensuing local ionic instability eventually spreads to the whole neuron and involves fascicula- tion-like spiking events. A shortage of ATP also causes a rise in intracellular calcium. Our modeling work supports the notion that mitochondrial dysfunction can account for salient features of the paralytic disorder amyotrophic lateral sclerosis, including motor neuron hyperexcitability, fascicula- tion, and differential vulnerability of motor neuron subpopulations.

11/02/2014 | Nat Commun   IF 11.3
Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction.
Israel JM, Cabelguen JM, Le Masson G, Oliet SH, Ciofi P

The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-alpha. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

29/11/2011 | Neurology   IF 8.2
Parkinson disease, L-dopa, and neuropathy: did we miss something?
Tison F, Le Masson G


16/11/2011 | J Neurosci   IF 5.9
State-dependent, bidirectional modulation of neural network activity by endocannabinoids.
Piet R, Garenne A, Farrugia F, Le Masson G, Marsicano G, Chavis P, Manzoni OJ

The endocannabinoid (eCB) system and the cannabinoid CB1 receptor (CB1R) play key roles in the modulation of brain functions. Although actions of eCBs and CB1Rs are well described at the synaptic level, little is known of their modulation of neural activity at the network level. Using microelectrode arrays, we have examined the role of CB1R activation in the modulation of the electrical activity of rat and mice cortical neural networks in vitro. We find that exogenous activation of CB1Rs expressed on glutamatergic neurons decreases the spontaneous activity of cortical neural networks. Moreover, we observe that the net effect of the CB1R antagonist AM251 inversely correlates with the initial level of activity in the network: blocking CB1Rs increases network activity when basal network activity is low, whereas it depresses spontaneous activity when its initial level is high. Our results reveal a complex role of CB1Rs in shaping spontaneous network activity, and suggest that the outcome of endogenous neuromodulation on network function might be state dependent.

11/2011 | PLoS Pathog   IF 7
Neurons are MHC class I-dependent targets for CD8 T cells upon neurotropic viral infection.
Chevalier G, Suberbielle E, Monnet C, Duplan V, Martin-Blondel G, Farrugia F, Le Masson G, Liblau R, Gonzalez-Dunia D

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage.

Deep dorsal horn relay neurons (dDHNs) of the spinal cord are known to exhibit multiple firing patterns under the control of local metabotropic neuromodulation: tonic firing, plateau potential, and spontaneous oscillations. This work investigates the role of interactions between voltage-gated channels and the occurrence of different firing patterns and then correlates these two phenomena with their functional role in sensory information processing. We designed a conductance-based model using the NEURON software package, which successfully reproduced the classical features of plateau in dDHNs, including a wind-up of the neuronal response after repetitive stimulation. This modeling approach allowed us to systematically test the impact of conductance interactions on the firing patterns. We found that the expression of multiple firing patterns can be reproduced by changes in the balance between two currents (L-type calcium and potassium inward rectifier conductances). By investigating a possible generalization of the firing state switch, we found that the switch can also occur by varying the balance of any hyperpolarizing and depolarizing conductances. This result extends the control of the firing switch to neuromodulators or to network effects such as synaptic inhibition. We observed that the switch between the different firing patterns occurs as a continuous function in the model, revealing a particular intermediate state called the accelerating mode. To characterize the functional effect of a firing switch on information transfer, we used correlation analysis between a model of peripheral nociceptive afference and the dDHN model. The simulation results indicate that the accelerating mode was the optimal firing state for information transfer.

08/2007 | J Virol   IF 4.6
Borna disease virus infection impairs synaptic plasticity.
Volmer R, Prat CM, Le Masson G, Garenne A, Gonzalez-Dunia D

The mechanisms whereby Borna disease virus (BDV) can impair neuronal function and lead to neurobehavioral disease are not well understood. To analyze the electrophysiological properties of neurons infected with BDV, we used cultures of neurons grown on multielectrode arrays, allowing a real-time monitoring of the electrical activity across the network shaped by synaptic transmission. Although infection did not affect spontaneous neuronal activity, it selectively blocked activity-dependent enhancement of neuronal network activity, one form of synaptic plasticity thought to be important for learning and memory. These findings highlight the original mechanism of the neuronal dysfunction caused by noncytolytic infection with BDV.

01/2007 | Eur J Neurosci   IF 3
L-type calcium channels and NMDA receptors: a determinant duo for short-term nociceptive plasticity.
Fossat P, Sibon I, Le Masson G, Landry M, Nagy F

In the dorsal horn of the spinal cord, pain-transmitting neurons exhibit action potential windup, a form of short-term plasticity, which consists of a progressive increase in neuronal response during repetitive stimulation of nociceptive input fibers. Windup depends on N-methyl-D-aspartate (NMDA) receptor activation, but previous in vitro studies indicated that windup also relies on intrinsic plateau properties of spinal neurons. In the present study, we considered the possible involvement of these properties in windup in vivo. For this purpose, we first studied a nociceptive flexion reflex in the rat. We showed that windup of the reflex is actually suppressed by blockers of L-type calcium current and Ca(2+)-activated non-specific cationic current (Ican), the two main depolarizing conductances of plateau potentials. We further showed that, during windup, NMDA receptors provide a critical excitatory component in a dynamic balance of excitatory and inhibitory inputs which ultimately activates L-type calcium channels. The nociceptive reflex involves at least two neuronal groups, which may express intrinsic amplification properties, motor neurons and dorsal horn neurons. By means of extracellular recordings in the dorsal horn, we showed that windup of dorsal horn neuron discharge was sensitive to the modulators of L-type calcium current. Altogether, our results suggest that, in vivo, windup also depends on the amplification properties of spinal neurons, the triggering of which requires previous activation of NMDA receptors.

2007 | Conf Proc IEEE Eng Med Biol Soc   IF 1.1
A real-time closed-loop setup for hybrid neural networks.
Bontorin G, Renaud S, Garenne A, Alvado L, Le Masson G, Tomas J

Hybrid living-artificial neural networks are an efficient and adaptable experimental support to explore the dynamics and the adaptation process of biological neural systems. We present in this paper an innovative platform performing a real-time closed-loop between a cultured neural network and an artificial processing unit like a robotic interface. The system gathers bioware, hardware, and software components and ensures the closed-loop data processing in less than 50 micros. We detail here the system components and compare its performances to a recent commercial platform.