Pascal Legendre

Pascal Legendre
French Institute of Health and Medical Research | Inserm · INSERM U1130 Paris, France

PhD

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115
Publications
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Publications

Publications (115)
Article
Survival of animals is dependent on the correct selection of an appropriate behavioral response to competing external stimuli. Theoretical models have been proposed and underlying mechanisms are emerging to explain how one circuit is selected among competing neural circuits. The evolutionarily conserved forebrain to midbrain habenulo-interpeduncula...
Article
In the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate and propagate action potentials. Accordingly, neuroepithelial progenitors (NEPs), which give rise to all neurons and glial cells during development, have been reported to remain electricall...
Article
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GABAA receptors are ligand-gated chloride channels and ionotropic receptors of GABA, the main inhibitory neurotransmit-ter in vertebrates. In this review, we discuss the major and diverse roles GABAA receptors play in the regulation of neuronal communication and the functioning of the brain. GABAA receptors have complex electrophysiological propert...
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Super-resolution imaging has revealed that key synaptic proteins are dynamically organized within sub-synaptic domains (SSDs). To examine how different inhibitory receptors are regulated, we carried out dual-color direct stochastic optical reconstruction microscopy (dSTORM) of GlyRs and GABAARs at mixed inhibitory synapses in spinal cord neurons. W...
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Renshaw cells (V1R) are excitable as soon as they reach their final location next to the spinal motoneurons and are functionally heterogeneous. Using multiple experimental approaches, in combination with biophysical modeling and dynamical systems theory, we analyzed, for the first time, the mechanisms underlying the electrophysiological properties...
Preprint
Full-text available
Super-resolution imaging of synapses has revealed that key synaptic proteins are dynamically organized within sub-synaptic domains (SSDs). At mixed inhibitory synapses in spinal cord neurons, both GlyRs and GABA A Rs reside at the same post-synaptic density (PSD). To examine how the different inhibitory receptors are organized and regulated, we car...
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While the role of cholinergic neurotransmission from motoneurons is well established during neuromuscular development, whether it regulates central nervous system development in the spinal cord is unclear. Zebrafish presents a powerful model to investigate how the cholinergic system is set up and evolves during neural circuit formation. In this stu...
Preprint
Full-text available
Spontaneous neuronal activity occurs at the onset of the synaptogenesis in the central Nervous System and plays a major role in shaping developing neural networks. How intrinsic properties of neurons evolve during this critical developmental period remains largely unknown. We studied the Renshaw cells because they participate to the early-synchroni...
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Astrocytes are a major type of glial cell in the mammalian brain, essentially regulating neuronal development and function. Quantitative imaging represents an important approach to study astrocytic signaling in neural circuits. Focusing on astrocytic Ca²⁺ activity, a key pathway implicated in astrocye-neuron interaction, we here report a strategy c...
Preprint
Full-text available
In the developing central nervous system, electrical signaling is thought to rely exclusively on differentiating neurons as they acquire the ability to generate action potentials. Accordingly, the neuroepithelial progenitors (NEPs) giving rise to all neurons and glial cells during development have been reported to remain electrically passive. Here,...
Article
In the last decade, tremendous progress has been made in understanding the biology of microglia - i.e. The fascinating immigrated resident immune cell population of the central nervous system (CNS). Recent literature reviews have largely dealt with the plentiful functions of microglia in CNS homeostasis, development and pathology, and the influence...
Article
Microglia are known to regulate several aspects of the development of the central nervous system. When microglia colonize the spinal cord, from E11.5 in the mouse embryo, they interact with growing central axons of dorsal root ganglion sensory neurons (SNs), which suggests that they may have some functions in SN development. To address this issue,...
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Spontaneous network activity (SNA) emerges in the spinal cord (SC) before the formation of peripheral sensory inputs and central descending inputs. SNA is characterized by recurrent giant depolarizing potentials (GDPs). Because GDPs in motoneurons (MNs) are mainly evoked by prolonged release of GABA, they likely necessitate sustained firing of inte...
Article
Virtually all oligodendrocyte precursors cells (OPCs) receive glutamatergic and/or GABAergic synapses that are lost upon their differentiation into oligodendrocytes in the postnatal and adult brain. Although OPCs are generated at mid‐embryonic stages, several weeks before the onset of myelination, it remains unknown when and where OPCs receive thei...
Article
Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the mic...
Article
Several studies have indicated that inflammation during pregnancy increases the risk for the development of neuropsychiatric disorders in the offspring. Morphological brain abnormalities combined with deviations in the inflammatory status of the brain can be observed in patients of both autism and schizophrenia. It was shown that acute infection ca...
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Full-text available
Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by marked genetic heterogeneity. Recent studies of rare structural and sequence variants have identified hundreds of loci involved in ASD, but our knowledge of the overall genetic architecture and the underlying pathophysiological mechanisms remains incomplete. Gl...
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Full-text available
Several studies have indicated that inflammation during pregnancy increases the risk for the development of neuropsychiatric disorders in the offspring. Morphological brain abnormalities combined with deviations in the inflammatory status of the brain can be observed in patients of both autism and schizophrenia. It was shown that acute infection ca...
Article
Full-text available
A remarkable feature of early neuronal networks is their endogenous ability to generate spontaneous rhythmic electrical activity independently of any external stimuli. In the mouse embryonic SC, this activity starts at an embryonic age of ∼12 d and is characterized by bursts of action potentials recurring every 2-3 min. Although these bursts have b...
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Microglia cells are the macrophages of the central nervous system with a crucial function in the homeostasis of the adult brain. However, recent studies showed that microglial cells may also have important functions during early embryonic central nervous system development. In this review we summarize recent works on the extra embryonic origin of m...
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11th European Meeting on Glial Cell Function in Health and Disease, Berlin, GERMANY, JUL 03-06, 2013
Conference Paper
11th European Meeting on Glial Cell Function in Health and Disease, Berlin, GERMANY, JUL 03-06, 2013
Article
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The axon initial segment (AIS) is responsible for both the modulation of action potentials and the maintenance of neuronal polarity. Yet, the molecular mechanisms controlling its assembly are incompletely understood. Our study in single electroporated motor neurons in mouse embryos revealed that AnkyrinG (AnkG), the AIS master organizer, is undetec...
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Glycine acts as a neuromodulator to regions rich of glutamatergic synapses, such as the forebrain. However, recent evidences for synaptic release of glycine in hippocampal cultured neurons and synaptosomes argue for the existence of functional glycinergic synapses in the hippocampus. It is well established that GABA and glycine act in concert at in...
Article
Microglia are the immune cells of the central nervous sys-tem. They are suspected to play important roles in adult synaptogenesis and in the development of the neuronal net-work. Microglial cells originate from progenitors in the yolk sac. Although it was suggested that they invade the cortex at early developmental stages in the embryo, their invas...
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DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR CHLORIDE ASSOCIATED WITH A SHIFT IN GABA POLARITY: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and pr...
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Microglia are known to invade the mammalian spinal cord (SC) at an early embryonic stage. While the mechanisms underlying this early colonization of the nervous system are still unknown, we recently found that it is associated, at least partially, with the ability of microglia to proliferate at the onset of motoneuron developmental cell death and o...
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It is a common and widely accepted assumption that glycine and GABA are the main inhibitory transmitters in the central nervous system (CNS). But, in the past 20years, several studies have clearly demonstrated that these amino acids can also be excitatory in the immature central nervous system. In addition, it is now established that both GABA rece...
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γ-aminobutyric acid (GABA) acting on Cl(-)-permeable ionotropic type A (GABA(A)) receptors (GABA(A)R) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the...
Article
Full-text available
Microglial cells invade the central nervous system during embryonic development, but their developmental functional roles in vivo remain largely unknown. Accordingly, their invasion pattern during early embryonic development is still poorly understood. To address this issue, we analyzed the initial developmental pattern of microglial cell invasion...
Conference Paper
Infection during pregnancy can lead to maternal inflammation. Several studies have suggested that maternal inflammation increases the risk on neuropsychiatric disorders, like autism, in the offspring. The cause of autism remains unknown, it is thought to be a complex interaction of different factors. A study of Vargas et al demonstrated the presenc...
Conference Paper
Like for other neurotransmitters, there is growing evidence that glycine, besides its classical role in fast inhibitory neurotransmission could play a role in paracrine communication within the central nervous system. Studies have shown that inhibitory neurotransmitters can have beneficial effects on neuronal precursor cells with respect to migrati...
Article
Full-text available
Rhythmic electrical activity is a hallmark of the developing embryonic CNS and is required for proper development in addition to genetic programs. Neurotransmitter release contributes to the genesis of this activity. In the mouse spinal cord, this rhythmic activity occurs after embryonic day 11.5 (E11.5) as waves spreading along the entire cord. At...
Article
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Information processing in the brain requires a delicate balance between excitation and inhibition. Glycine receptors (GlyR) are involved in inhibitory mechanisms mainly at a synaptic level, but potential novel roles for these receptors recently emerged due to the discovery of posttranscriptional processing. GLR transcripts are edited through enzyma...
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Glycine receptor (GlyR) alpha3 is involved in vision, and processing of acoustic and nociceptive signals, and RNA editing of GLRA3 transcripts was associated with hippocampal pathophysiology of mesial temporal lobe epilepsy (TLE). However, neither the role of GlyR alpha3 splicing in hippocampal neurons nor the expression of splice variants have yet...
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An increasing number of epilepsy patients are afflicted with drug-resistant temporal lobe epilepsy (TLE) and require alternative therapeutic approaches. High-affinity glycine receptors (haGlyRs) are functionally adapted to tonic inhibition due to their response to hippocampal ambient glycine, and their synthesis is activity-dependent. Therefore, in...
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The spinal dorsal horn (SDH) is the first step in the integration of primary nociceptive information, which is controlled by the descending serotonin (5-HT) system as well as the principal inhibitory neurotransmitter gamma-aminobutyric acid (GABA). However, the influence exerted by 5-HT on GABA synthesis remains poorly understood. The major pathway...
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In the hypoglossal nucleus of wild-type mice, early mixed glycinergic-GABAergic inhibitory transmission becomes mainly glycinergic during postnatal maturation. In spastic mice (SPA), a model of human hyperekplexic syndrome, an insertion into the gene of the glycine receptor (GlyR) beta subunit results in a decreased accumulation of GlyRs at postsyn...
Article
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Glycine and GABA mediate inhibitory neurotransmission in the spinal cord and central nervous system. The general concept of neurotransmission is now challenged by the contribution of both phasic activation of postsynaptic glycine and GABA(A) receptors (GlyRs and GABA(A)Rs, respectively) and tonic activity of these receptors located at extrasynaptic...
Article
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Contrary to its effect on the gamma-aminobutyric acid type A and C receptors, picrotoxin antagonism of the alpha1 homomeric glycine receptors (GlyRs) has been shown to be non-use-dependent and nonselective between the picrotoxin components picrotoxinin and picrotin. Picrotoxin antagonism of the embryonic alpha2 homomeric GlyR is known to be use-dep...
Article
Full-text available
Contrary to its effect on the -aminobutyric acid type A and C receptors, picrotoxin antagonism of the a1 homomeric glycine receptors (GlyRs) has been shown to be non-use-dependent and non-selective between the picrotoxin components picrotoxinin and picrotin. Picrotoxin antagonism of the embryonic a2 homomeric GlyR is known to be use-dependent, refl...
Article
At postsynaptic densities of mouse hypoglossal motoneurons, the proportion of glycine receptors co-clustered with GABAA receptors increases from neonatal to adult animals, suggesting that mixed synapses might play a greater role in adult synaptic inhibition. We visualized the presynaptic correlates of these developmental changes using immunocytoche...
Article
In vertebrates, most glycinergic inhibitory neurons discharge phasically at a relatively low frequency. Such a pattern of glycine liberation from presynaptic terminals may affect the kinetics of post-synaptic glycine receptors. To examine this influence, we have analyzed the behavior of glycine receptors in response to repetitive stimulation at fre...
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It is well known that the convulsant alkaloid picrotoxin (PTX) can inhibit neuronal gamma-aminobutyric acid (GABA) and homomeric glycine receptors (GlyR). However, the mechanism for PTX block of alpha(2) homomeric GlyR is still unclear compared with that of alpha(1) homomeric GlyR, GABA(A), and GABA(C) receptors. Furthermore, PTX effects on GlyR ki...
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In this work, we show that beta-carbolines, which are known negative allosteric modulators of GABA(A) receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In both cell types, beta-carboline-induced inhibition of glycine receptor (GlyR)-mediated responses decreases with time in culture. Single-channel r...
Article
In the hypoglossal nucleus, GABA and glycine mediate inhibition at separate or mixed synapses containing glycine receptors (GlyRs) and/or GABA(A) receptors (GABA(A)Rs). The functional development of mixed inhibitory synapses depends on the brain area studied, but their relative proportion to total synapses generally decreases with time. We have det...
Article
Ionotropic glycine receptors (GlyRs) are present in the central nervous system well before the establishment of synaptic contacts. Immature nerve cells are known, at least in the spinal cord, to express alpha2 homomeric GlyRs, the properties of which are relatively unknown compared to those of the adult synaptic form of the GlyR (mainly alpha1/beta...
Article
Full-text available
In the hypoglossal nucleus, GABA and glycine mediate inhibition at separate or mixed synapses containing glycine receptors (GlyRs) and/or GABA(A) receptors (GABA(A)Rs). The functional development of mixed inhibitory synapses depends on the brain area studied, but their relative proportion to total synapses generally decreases with time. We have det...
Article
The amplitude of glycinergic miniature inhibitory postsynaptic currents (mIPSCs) varies considerably in neurons recorded in the isolated hindbrain of 50-h-old zebrafish larvae. At this age, glycinergic synapses are functionally mature. In order to measure the occupancy level of postsynaptic glycine receptors (GlyRs) and to determine the pre- and/or...
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Presynaptic nerve terminals of inhibitory synapses in the dorsal horn of the spinal cord and brain stem can release both GABA and glycine, leading to coactivation of postsynaptic GABAA and glycine receptors. In the present study we have analyzed functional interactions between GABAA and glycine receptors in acutely dissociated neurons from rat sacr...