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Dive into the research topics where Hélène Bras is active.

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Featured researches published by Hélène Bras.


Nature Medicine | 2010

Down-regulation of the potassium-chloride cotransporter KCC2 contributes to spasticity after spinal cord injury

Pascale Boulenguez; Sylvie Liabeuf; Rémi Bos; Hélène Bras; Céline Jean-Xavier; Cécile Brocard; Aurélie Stil; Pascal Darbon; Daniel Cattaert; Eric Delpire; Martin Marsala; Laurent Vinay

Hyperexcitability of spinal reflexes and reduced synaptic inhibition are commonly associated with spasticity after spinal cord injury (SCI). In adults, the activation of γ-aminobutyric acidA (GABAA) and glycine receptors inhibits neurons as a result of low intracellular chloride (Cl−) concentration, which is maintained by the potassium-chloride cotransporter KCC2 (encoded by Slc12a5). We show that KCC2 is downregulated after SCI in rats, particularly in motoneuron membranes, thereby depolarizing the Cl− equilibrium potential and reducing the strength of postsynaptic inhibition. Blocking KCC2 in intact rats reduces the rate-dependent depression (RDD) of the Hoffmann reflex, as is observed in spasticity. RDD is also decreased in KCC2-deficient mice and in intact rats after intrathecal brain-derived neurotrophic factor (BDNF) injection, which downregulates KCC2. The early decrease in KCC2 after SCI is prevented by sequestering BDNF at the time of SCI. Conversely, after SCI, BDNF upregulates KCC2 and restores RDD. Our results open new perspectives for the development of therapeutic strategies to alleviate spasticity.


Proceedings of the National Academy of Sciences of the United States of America | 2013

Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2

Rémi Bos; Karina Sadlaoud; Pascale Boulenguez; Dorothée Buttigieg; Sylvie Liabeuf; Cécile Brocard; Georg Haase; Hélène Bras; Laurent Vinay

In healthy adults, activation of γ-aminobutyric acid (GABA)A and glycine receptors inhibits neurons as a result of low intracellular chloride concentration ([Cl–]i), which is maintained by the potassium-chloride cotransporter KCC2. A reduction of KCC2 expression or function is implicated in the pathogenesis of several neurological disorders, including spasticity and chronic pain following spinal cord injury (SCI). Given the critical role of KCC2 in regulating the strength and robustness of inhibition, identifying tools that may increase KCC2 function and, hence, restore endogenous inhibition in pathological conditions is of particular importance. We show that activation of 5-hydroxytryptamine (5-HT) type 2A receptors to serotonin hyperpolarizes the reversal potential of inhibitory postsynaptic potentials (IPSPs), EIPSP, in spinal motoneurons, increases the cell membrane expression of KCC2 and both restores endogenous inhibition and reduces spasticity after SCI in rats. Up-regulation of KCC2 function by targeting 5-HT2A receptors, therefore, has therapeutic potential in the treatment of neurological disorders involving altered chloride homeostasis. However, these receptors have been implicated in several psychiatric disorders, and their effects on pain processing are controversial, highlighting the need to further investigate the potential systemic effects of specific 5-HT2AR agonists, such as (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide (TCB-2).


European Journal of Neuroscience | 1994

Electrotonic Clusters in the Dendritic Arborization of Abducens Motoneurons of the Rat

S. M. Korogod; Hélène Bras; V. N. Sarana; Paul Gogan; Suzanne Tyc-Dumont

Following reconstruction with high spatial resolution of the 3‐D geometry of the dendritic arborizations of two abducens motoneurons, we simulated the distribution of electrotonic voltage over the whole dendritic tree. Here, we demonstrate that the complex stochastic electrotonic structure of both motoneurons can be reduced to a statistically significant small set of well discriminated clusters. These clusters are formed by dendritic branches belonging to different dendrites of the neuron but with similar electrotonic properties. A cluster analysis was performed to estimate quantitatively the partition of the branches between the dendritic clusters. The contents of the clusters were analysed in relation to their stability under different values of specific membrane resistivity (Rm), to their remoteness from the soma and their location in 3‐D space. The cluster analysis was executed in a 2‐D parameter space in which each dendritic branch was described by the mean electrotonic voltage and gradient. The number of clusters was found to be four for each motoneuron when computations were made with Rm= 3 kΩ.cm2. An analysis of the cluster composition under different Rm revealed that each cluster contained invariant and variant branches. Mapping the clusters upon the dendritic geometry of the arborizations allowed us to describe the cluster distribution in terms of the 3‐D space domain, the 2‐D path distance domain and the total surface area of the tree. As the cluster behaviour reflects both the geometry and the changes in the neuronal electrotonic structure, we conclude that cluster analysis provides a tool to handle the functional complexity of the arborizations without losing relevant information. In terms of synaptic activities, the stable dendritic branches in each cluster may process the synaptic inputs in a similar manner. The high percentage of stable branches indicates that geometry is a major factor of stability for the electrotonic clusters. Conversely, the variant branches introduce the conditions for mechanisms of functional postsynaptic plasticity.


European Journal of Neuroscience | 2006

Differential expression of GABAA and glycine receptors in ALS-resistant vs. ALS-vulnerable motoneurons: possible implications for selective vulnerability of motoneurons

Louis-Etienne Lorenzo; Annick Barbe; Paule Portalier; Jean-Marc Fritschy; Hélène Bras

Amyotrophic lateral sclerosis (ALS) is a devastating motoneuronal degenerative disease, which is inevitably fatal in adults. ALS is characterized by an extensive loss of motoneurons in the cerebrospinal axis, except for those motoneurons that control eye movements and bladder contraction. The reason for this selectivity is not known. Systematic differences have been found in the organization of excitatory synaptic transmission in ALS‐resistant vs. ALS‐susceptible motor nuclei. However, although motoneurons express high levels of glycine receptors (GlyR) and GABAA receptors (GABAAR), no such studies have been carried out yet for inhibitory synaptic transmission. In this study, we compared the subunit composition, patterns of expression, density and synaptic localization of inhibitory synaptic receptors in ALS‐resistant (oculomotor, trochlear and abducens) and ALS‐vulnerable motoneurons (trigeminal, facial and hypoglossi). Triple immunofluorescent stainings of the major GABAAR subunits (α1, α2, α3, and α5), the GlyR α1 subunit and gephyrin, were visualized by confocal microscopy and analysed quantitatively. A strong correlation was observed between the vulnerability of motoneurons and the subunit composition of GABAAR, the GlyR/GABAAR density ratios and the incidence of synaptic vs. extrasynaptic GABAAR. These differences contrast strikingly with the uniform gephyrin cluster density and synaptic GlyR levels recorded in all motor nuclei examined. These results suggest that the specific patterns of inhibitory receptor organization observed might reflect functional differences that are relevant to the physiopathology of ALS.


European Journal of Neuroscience | 1993

Stochastic Geometry and Electrotonic Architecture of Dendritic Arborization of Brain Stem Motoneuron

Hélène Bras; S. M. Korogod; Y. Driencourt; Paul Gogan; Suzanne Tyc-Dumont

We describe how the stochastic geometry of dendritic arborization of a single identified motoneuron of the rat affects the local details of its electrotonic structure. After describing the 3D dendritic geometry at high spatial resolution, we simulate the distribution of voltage gradients along dendritic branches under steady‐state and transient conditions. We show that local variations in diameters along branches and asymmetric branchings determine the non‐monotonous features of the heterogeneous electrotonic structure. This is defined by the voltage decay expressed as a function of the somatofugal paths in physical distances (voltage gradient). The fan‐shaped electrotonic structure demonstrates differences between branches which are preserved when simulations are computed from different values of specific membrane resistivity although the absolute value of their voltages is changed. At given distances from soma and over long paths, some branches display similar voltages resulting in their grouping which is also preserved when specific membrane resistivity is changed. However, the mutual relation between branches inside the group is respecified when different values of specific membrane resistivity are used in the simulations. We find that there are some invariant features of the electrotonic structure which are related to the geometry and not to the electrical parameters, while other features are changed by altering the electrical parameters. Under transient conditions, the somatofugal invasion of the dendritic tree by a somatic action potential shifts membrane potentials (above 10 mV) of dendritic paths for unequal distances from the soma during several milliseconds. Electrotonic reconfigurations and membrane shifts might be a mechanism for postsynaptic plasticity.


The Journal of Comparative Neurology | 2011

Characterization of last-order premotor interneurons by transneuronal tracing with rabies virus in the neonatal mouse spinal cord

Patrice Coulon; Hélène Bras; Laurent Vinay

We characterized the interneurons involved in the control of ankle extensor (triceps surae [TS] muscles) motoneurons (MNs) in the lumbar enlargement of mouse neonates by retrograde transneuronal tracing using rabies virus (RV). Examination of the kinetics of retrograde transneuronal transfer at sequential intervals post inoculation enabled us to determine the time window during which only the first‐order interneurons, i.e., interneurons likely monosynaptically connected to MNs (last‐order interneurons [loINs]) were RV‐infected. The infection of the network resulted exclusively from a retrograde transport of RV along the motor pathway. About 80% of the loINs were observed ipsilaterally to the injection. They were distributed all along the lumbar enlargement, but the majority was observed in L4 and L5 segments where TS MNs were localized. Most loINs were distributed in laminae V–VII, whereas the most superficial laminae were devoid of RV infection. Contralaterally, commissural loINs were found essentially in lamina VIII of all lumbar segments. Groups of loINs were characterized by their chemical phenotypes using dual immunolabeling. Glycinergic neurons connected to TS MNs represented 50% of loINs ipsilaterally and 10% contralaterally. As expected, the ipsilateral glycinergic loINs included Renshaw cells, the most ventral neurons expressing calbindin. We also demonstrated a direct connection between a group of cholinergic interneurons observed ipsilaterally in L3 and the rostral part of L4, and TS MNs. To conclude, transneuronal tracing with RV, combined with an immunohistochemical detection of neuronal determinants, allows a very specific mapping of motor networks involved in the control of single muscles. J. Comp. Neurol. 519:3470–3487, 2011.


The Journal of Neuroscience | 2010

Differential Plasticity of the GABAergic and Glycinergic Synaptic Transmission to Rat Lumbar Motoneurons after Spinal Cord Injury

Karina Sadlaoud; Sabrina Tazerart; Cécile Brocard; Céline Jean-Xavier; Paule Portalier; Frédéric Brocard; Laurent Vinay; Hélène Bras

Maturation of inhibitory postsynaptic transmission onto motoneurons in the rat occurs during the perinatal period, a time window during which pathways arising from the brainstem reach the lumbar enlargement of the spinal cord. There is a developmental switch in miniature IPSCs (mIPSCs) from predominantly long-duration GABAergic to short-duration glycinergic events. We investigated the effects of a complete neonatal [postnatal day 0 (P0)] spinal cord transection (SCT) on the expression of Glycine and GABAA receptor subunits (GlyR and GABAAR subunits) in lumbar motoneurons. In control rats, the density of GlyR increased from P1 to P7 to reach a plateau, whereas that of GABAAR subunits dropped during the same period. In P7 animals with neonatal SCT (SCT-P7), the GlyR densities were unchanged compared with controls of the same age, while the developmental downregulation of GABAAR was prevented. Whole-cell patch-clamp recordings of mIPSCs performed in lumbar motoneurons at P7 revealed that the decay time constant of miniature IPSCs and the proportion of GABAergic events significantly increased after SCT. After daily injections of the 5-HT2R agonist DOI, GABAAR immunolabeling on SCT-P7 motoneurons dropped down to values reported in control-P7, while GlyR labeling remained stable. A SCT made at P5 significantly upregulated the expression of GABAAR 1 week later with little, if any, influence on GlyR. We conclude that the plasticity of GlyR is independent of supraspinal influences whereas that of GABAAR is markedly influenced by descending pathways, in particular serotoninergic projections.


Journal of Physiology-paris | 1999

Gating of action potential propagation by an axonal A-like potassium conductance in the hippocampus: A new type of non-synaptic plasticity

Dominique Debanne; Irina L. Kopysova; Hélène Bras; Nadine Ferrand

Synaptic plasticity is usually considered as the main form of activity-dependent functional plasticity in the mammalian brain. Short- and long-term regulation of synaptic transmission have been shown in various types of excitatory synapses including cortical and hippocampal synapses. In this review, we discuss a novel form of non-synaptic plasticity that involves voltage-gated K+ conductances in CA3 pyramidal cell axons. With experimental and theoretical arguments, we show that axons cannot only be considered as a simple structure that transmit reliably the action potential (AP) from the cell body to the nerve terminals. The axon is also able to express conduction failures in specific axonal pathways. We discuss possible physiological conditions in which these axonal plasticity may occur and its incidence on hippocampal network properties.


Neuroscience Letters | 1996

Evidence for colocalization of GABA and glycine in afferents to retrogradely labelled rat abducens motoneurones

Fatiha Lahjouji; Annick Barbe; Geneviève Chazal; Hélène Bras

The coexistence of gamma-aminobutyric acid (GABA) and glycine in axon terminals impinging on rat abducens motoneurones was investigated using a double staining procedure combining retrograde labelling of the motoneurones with HRP and post-embedding immunocytochemical staining of axon terminals. Adjacent ultrathin sections of cell bodies of identified motoneurones were individually treated with GABA or glycine antibodies. The terminals single labelled for GABA represented 11.4% of the terminals analyzed, while 8% of them were glycine immunoreactive and 9% were both GABA and glycine immunoreactive. All the labelled terminals contained pleomorphic vesicles. The mean length of apposition of the double labelled terminals was statistically larger (2.20 +/- 0.97 microns) than the GABA (1.65 +/- 0.57 microns) or glycine immunoreactive ones (1.37 +/- 0.35 microns).


European Journal of Neuroscience | 2008

Prenatal activation of 5‐HT2A receptor induces expression of 5‐HT1B receptor in phrenic motoneurons and alters the organization of their premotor network in newborn mice

Hélène Bras; Susana P. Gaytán; Paule Portalier; Sébastien Zanella; Rosario Pasaro; Patrice Coulon; Gérard Hilaire

In newborn mice of the control [C3H/HeJ (C3H)] and monoamine oxidase A‐deficient (Tg8) strains, in which levels of endogenous serotonin (5‐HT) were drastically increased, we investigated how 5‐HT system dysregulation affected the maturation of phrenic motoneurons (PhMns), which innervate the diaphragm. First, using immunocytochemistry and confocal microscopy, we observed a 5‐HT2A receptor (5‐HT2A‐R) expression in PhMns of both C3H and Tg8 neonates at the somatic and dendritic levels, whereas 5‐HT1B receptor (5‐HT1B‐R) expression was observed only in Tg8 PhMns at the somatic level. We investigated the interactions between 5‐HT2A‐R and 5‐HT1B‐R during maturation by treating pregnant C3H mice with a 5‐HT2A‐R agonist (2,5‐dimethoxy‐4‐iodoamphetamine hydrochloride). This pharmacological overactivation of 5‐HT2A‐R induced a somatic expression of 5‐HT1B‐R in PhMns of their progeny. Conversely, treatment of pregnant Tg8 mice with a 5‐HT2A‐R antagonist (ketanserin) decreased the 5‐HT1B‐R density in PhMns of their progeny. Second, using retrograde transneuronal tracing with rabies virus injected into the diaphragm of Tg8 and C3H neonates, we studied the organization of the premotor network driving PhMns. The interneuronal network monosynaptically connected to PhMns was much more extensive in Tg8 than in C3H neonates. However, treatment of pregnant C3H mice with 2,5‐dimethoxy‐4‐iodoamphetamine hydrochloride switched the premotoneuronal network of their progeny from a C3H‐ to a Tg8‐like pattern. These results show that a prenatal 5‐HT excess affects, via the overactivation of 5‐HT2A‐R, the expression of 5‐HT1B‐R in PhMns and the organization of their premotor network.

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Annick Barbe

Centre national de la recherche scientifique

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Laurent Vinay

Aix-Marseille University

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Laurent Vinay

Aix-Marseille University

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Patrice Coulon

Aix-Marseille University

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Cécile Brocard

Centre national de la recherche scientifique

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Fatiha Lahjouji

Centre national de la recherche scientifique

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Pascale Boulenguez

Centre national de la recherche scientifique

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Patrice Coulon

Aix-Marseille University

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Paul Gogan

Centre national de la recherche scientifique

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