Showing papers by "Collège de France published in 2010"
TL;DR: H hippocampal/prefrontal coherence could lead to synchronization of reward predicting activity in prefrontal networks, tagging it for subsequent memory consolidation in rats learning new rules on a Y maze.
726 citations
TL;DR: Dynamic aspects of interactions between astrocytes, neurons and the vasculature have recently been in the neuroscience spotlight and this intercellular communication between glia has implications for neuroglial and gliovascular interactions.
Abstract: Dynamic aspects of interactions between astrocytes, neurons and the vasculature have recently been in the neuroscience spotlight. It has emerged that not only neurons but also astrocytes are organized into networks. Whereas neuronal networks exchange information through electrical and chemical synapses, astrocytes are interconnected through gap junction channels that are regulated by extra- and intracellular signals and allow exchange of information. This intercellular communication between glia has implications for neuroglial and gliovascular interactions and hence has added another level of complexity to our understanding of brain function.
682 citations
TL;DR: In this paper, a transcriptome analysis of retinal endothelial cells isolated from DLL4+/− and wild-type mice was performed to identify three clusters of tip cell-enriched genes encoding extracellular matrix degrading enzymes, basement membrane components and secreted molecules.
396 citations
TL;DR: Fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling are summarized.
Abstract: Endothelial cells (ECs) form extensive, highly branched and hierarchically organized tubular networks in vertebrates to ensure the proper distribution of molecular and cellular cargo in the vertebrate body. The growth of this vascular system during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of endothelial cells in a process termed angiogenesis. Surprisingly, specialized ECs, so-called tip cells, which lead and guide endothelial sprouts, share many feature with another guidance structure, the axonal growth cone. Tip cells are motile, invasive and extend numerous filopodial protrusions sensing growth factors, extracellular matrix and other attractive or repulsive cues in their tissue environment. Axonal growth cones and endothelial tip cells also respond to signals belonging to the same molecular families, such as Slits and Roundabouts, Netrins and UNC5 receptors, Semaphorins, Plexins and Neuropilins, and Eph receptors and ephrin ligands. Here we summarize fundamental principles of angiogenic growth, the selection and function of tip cells and the underlying regulation by guidance cues, the Notch pathway and vascular endothelial growth factor signaling.
373 citations
TL;DR: In this paper, Nitrogen-doped carbons were produced using hydrothermal carbonization of nitrogen-containing carbohydrates under mild temperature (180 °C) and the resulting materials contain significant amounts of nitrogen and display a high degree of aromatization.
369 citations
TL;DR: The half-wave potential is proposed as reference potential for the determination of overpotential values for H(2)-evolving catalysts in non-aqueous solvents and the formulas to which the measured potential should be compared are derived, taking into account the effect of homoconjugation.
Abstract: In an effort to standardize the determination of overpotential values for H2-evolving catalysts in non-aqueous solvents and allow a reliable comparison of catalysts prepared and assayed by different groups, we propose to adopt the half-wave potential as reference potential. We provide a simple method for measuring it from usual stationary cyclic voltammograms, and we derive the formulas to which the measured potential should be compared, taking into account the effect of homoconjugation. We also revisit tabulated values of the standard reduction potential of protons in non-aqueous solvents, EH+/H2°.
351 citations
TL;DR: A new mechanism of alternative glioblastoma vascularization is described and a new perspective for the antivascular treatment strategy is opened.
Abstract: Glioblastoma is one of the most angiogenic human tumours and endothelial proliferation is a hallmark of the disease. A better understanding of glioblastoma vasculature is needed to optimize anti-angiogenic therapy that has shown a high but transient efficacy. We analysed human glioblastoma tissues and found non-endothelial cell-lined blood vessels that were formed by tumour cells (vasculogenic mimicry of the tubular type). We hypothesized that CD133+ glioblastoma cells presenting stem-cell properties may express pro-vascular molecules allowing them to form blood vessels de novo. We demonstrated in vitro that glioblastoma stem-like cells were capable of vasculogenesis and endothelium-associated genes expression. Moreover, a fraction of these glioblastoma stem-like cells could transdifferentiate into vascular smooth muscle-like cells. We describe here a new mechanism of alternative glioblastoma vascularization and open a new perspective for the antivascular treatment strategy.
310 citations
TL;DR: There is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.
Abstract: Bacteria coordinate expression of virulence determinants in response to localized microenvironments in their hosts. Here we show that Shigella flexneri, which causes dysentery, encounters varying oxygen concentrations in the gastrointestinal tract, which govern activity of its type three secretion system (T3SS). The T3SS is essential for cell invasion and virulence. In anaerobic environments (for example, the gastrointestinal tract lumen), Shigella is primed for invasion and expresses extended T3SS needles while reducing Ipa (invasion plasmid antigen) effector secretion. This is mediated by FNR (fumarate and nitrate reduction), a regulator of anaerobic metabolism that represses transcription of spa32 and spa33, virulence genes that regulate secretion through the T3SS. We demonstrate there is a zone of relative oxygenation adjacent to the gastrointestinal tract mucosa, caused by diffusion from the capillary network at the tips of villi. This would reverse the anaerobic block of Ipa secretion, allowing T3SS activation at its precise site of action, enhancing invasion and virulence.
293 citations
TL;DR: In this paper, the authors highlight some of the main research accomplishments of nanomaterials and highlight the importance of the control of the hybrid interfaces via the use of modern tools such as DOSY NMR, SAXS, WAXS and Ellipsometry.
281 citations
TL;DR: It is suggested that, rather than providing a single common function, the two hippocampi provide complementary representations for navigation, concerning places on the right and temporal sequences on the left, both of which likely contribute to different aspects of episodic memory.
Abstract: The hippocampus is crucial for both spatial navigation and episodic memory, suggesting that it provides a common function to both. Here we adapt a spatial paradigm, developed for rodents, for use with functional MRI in humans to show that activation of the right hippocampus predicts the use of an allocentric spatial representation, and activation of the left hippocampus predicts the use of a sequential egocentric representation. Both representations can be identified in hippocampal activity before their effect on behavior at subsequent choice-points. Our results suggest that, rather than providing a single common function, the two hippocampi provide complementary representations for navigation, concerning places on the right and temporal sequences on the left, both of which likely contribute to different aspects of episodic memory.
252 citations
TL;DR: In this article, the role of every reactant in the nucleation and growth of the nanoparticles has been delineated: OA is the reductant and thus controls nucleation rate, while TOP provides a tunable surface stabilization through coordination on the Ni(0) surface.
Abstract: We present here a complete study on a synthesis of nickel nanoparticles involving the reaction of [Ni(acac)2] with oleylamine (OA) and trioctylphosphine (TOP) reactants, whose simultaneous presence and relative amounts are paramount. The role of every reactant in the nucleation and growth of the nanoparticles has been delineated: OA is the reductant and thus controls the nucleation rate, meanwhile TOP provides a tunable surface stabilization through coordination on the Ni(0) surface. This result leads us to a design synthesis providing tailored monodispersed nanoparticles in a wide range (2−30 nm), which allows self-consistent studies of size-induced changes in catalytic and magnetic properties. Additionally, the growth mechanism is demonstrated to include an aggregation step which thus correlates with the polycrystalline feature of the nanoparticles obtained through this process. Moreover, the critical influence of the phosphine in this system was demonstrated a) for the outcome of the ripening mechanism...
TL;DR: The early embryonic lethality seen in PRR-null mice suggests PRR has additional essential cellular functions the authors do not understand, and definitive proof is still lacking for a role for PRR in disease, or by showing improvement of disease by tissue-specific ablation of PRR or by administration of a specific PRR antagonist.
Abstract: The (pro)renin receptor (PRR) binds renin and prorenin, its proenzyme inactive form. Receptor-bound prorenin becomes enzymatically active and binding then activates the MAP kinases ERK1/2 and p38 pathways, leading to upregulation of profibrotic and cyclooxygenase-2 genes independent of angiotensin II generation. These characteristics explain the interest in the potential role of PRR in organ damage in diseases associated with activation of the renin-angiotensin system (RAS), in particular hypertension and diabetes. Although identification of PRR has improved our understanding of the physiology of the tissue RAS, its role in pathology is far from clear. Transgenic animals overexpressing PRR ubiquitously or selectively in smooth-muscle cells develop high BP or glomerulosclerosis, and increased expression of PRR is reported in models of hypertension or kidney damage. However, definitive proof is still lacking for a role for PRR in disease, or by showing improvement of disease by tissue-specific ablation of PRR or by administration of a specific PRR antagonist. Furthermore, the early embryonic lethality seen in PRR-null mice suggests PRR has additional essential cellular functions we do not understand.
TL;DR: This paper provides some correlation between the molecular structure of precursors in the solution and the nanostructure of the solid phases obtained by hydrothermal treatment of vanadium oxides.
Abstract: A wide range of vanadium oxides have been obtained via the hydrothermal treatment of aqueous V(V) solutions. They exhibit a large variety of nanostructures ranging from molecular clusters to 1D and 2D layered compounds. Nanotubes are obtained via a self-rolling process while amazing morphologies such as nano-spheres, nano-flowers and even nano-urchins are formed via the self-assembling of nano-particles. This paper provides some correlation between the molecular structure of precursors in the solution and the nanostructure of the solid phases obtained by hydrothermal treatment.
TL;DR: In this article, the role of electronic Coulomb correlations in superconductors is investigated and theoretical evidence for strong correlation effects in FeSe is provided based on dynamical mean field calculations.
Abstract: The role of electronic Coulomb correlations in iron-based superconductors is an important open question. We provide theoretical evidence for strong correlation effects in FeSe, based on dynamical mean field calculations. Our ab initio spectral properties first demonstrate the existence of a lower Hubbard band. Moreover, together with significant orbital-dependent mass enhancements, we find that the normal state is a bad metal over an extended temperature range, implying a non-Fermi liquid due to formation of local moments. Predictions for angle-resolved photoemission spectroscopy are made.
TL;DR: In this article, the authors show how a chemist can take the naturally occurring multi-electron catalysts for these two electro and photochemical reactions, photosystem II and hydrogenases, as a source of inspiration for the design of original, efficient and robust molecular catalysts.
Abstract: Photoelectrocatalytic cells for water splitting should combine one or two photosensitive units with a water oxidation catalyst at the anode and a hydrogen evolution catalyst at the cathode. In this perspective article, we first show how a chemist can take the naturally occurring multi-electron catalysts for these two electro- and photochemical reactions, photosystem II and hydrogenases, as a source of inspiration for the design of original, efficient and robust molecular catalysts. The focus of this article is given to the immobilisation of these natural or bio-inspired catalysts onto conducting surfaces and the design of electrode and photoelectrode materials for hydrogen evolution/uptake and water oxidation.
TL;DR: Evidence is provided for the selective involvement of the posterior parietal cortex and associated frontal regions in the specific process of egocentric localization of visual and somatosensory stimuli with respect to relevant body parts.
Abstract: We review human functional neuroimaging studies that have explicitly investigated the reference frames used in different cortical regions for representing spatial locations of objects. Beyond the general distinction between “egocentric” and “allocentric” reference frames, we provide evidence for the selective involvement of the posterior parietal cortex and associated frontal regions in the specific process of egocentric localization of visual and somatosensory stimuli with respect to relevant body parts (“body referencing”). Similarly, parahippocampal and retrosplenial regions, together with specific parietal subregions such as the precuneus, are selectively involved in a specific form of allocentric representation in which object locations are encoded relative to enduring spatial features of a familiar environment (“environmental referencing”). We also present a novel functional magnetic resonance imaging study showing that these regions are selectively activated, whenever a purely perceptual spatial task involves an object which maintains a stable location in space during the whole experiment, irrespective of its perceptual features and its orienting value as a landmark. This effect can be dissociated from the consequences of an explicit memory recall of landmark locations, a process that further engages the retrosplenial cortex.
TL;DR: In this article, a graphitic carbon nitride mpg-C3N4 infiltrated with a borane complex is pyrolyzed to yield boron carbon nitrides with very high surface areas up to 1560m2g−1.
Abstract: Nano- and mesoporous boron carbon nitrides with very high surface areas up to 1560 m2 g−1 are obtained by pyrolysis of a graphitic carbon nitride mpg-C3N4 infiltrated with a borane complex. This reactive hard-templating approach provides easy composition and texture tuning by temperature adjustment between 800 and 1400 °C. The process yields BxCyNzOvHw materials as direct copies of the initial template with controlled compositions of 0.15 ≤ x ≤ 0.36, 0.10 ≤ y ≤ 0.12, 0.14 ≤ z ≤ 0.32, and 0.11 ≤ v ≤ 0.28. The nano and mesoporosities can also be tuned in order to provide hierarchical materials with specific surface areas ranging from 610 to 1560 m2 g−1. Such high values, coupled with resistance against air oxidation up to 700 °C, suggest potential materials for gas storage and as catalyst supports. Indeed, it is demonstrated that these compounds exhibit high and tunable H2 uptakes from 0.55 to 1.07 wt.% at 77 K and 1 bar, thus guiding further search of materials for hydrogen storage.
TL;DR: It is demonstrated that inflammation-induced astroglial hemichannel activation plays a critical role in neuronal death and suggest a neuroprotective role of connexin43 hemichannels blockade.
TL;DR: In this article, the authors report processing of a thin film by chemical solution deposition of a microporous ZIF-8 nanoparticle dispersion, which shows a dual hierarchical porous structure from the micropores of the framework and the mesoporous interparticular voids.
Abstract: We report processing of a thin film by chemical solution deposition of a microporous ZIF-8 nanoparticle dispersion. By using the drain and capillary regimes involved in the dip-coating process, we tuned the thickness of the films from 40 nm to 1 μm and controlled the packing of the nanoparticles on the substrate. The high optical quality thin films show a dual hierarchical porous structure from the micropores of the framework and the mesoporous interparticular voids. Moreover, vapor sorption properties of the microporous ZIF-8 based thin films have been evaluated by ellipsometric porosimetry. The hydrophobic films show alcohol, THF and hydrocarbon adsorption. Experiments for isopropanol/water separation have been carried out and the selective adsorption of the alcohol versus the water makes these thin films good candidates for vapor sensors.
TL;DR: It is reported that exogenous estrogen replacement to ovariectomised mice in the absence of ERβ actually delayed wound healing, indicating clear uncoupling of inflammation and overall efficiency of repair.
Abstract: Post-menopausal women have an increased risk of developing a number of degenerative pathological conditions, linked by the common theme of excessive inflammation. Systemic estrogen replacement (in the form of hormone replacement therapy) is able to accelerate healing of acute cutaneous wounds in elderly females, linked to its potent antiinflammatory activity. However, in contrast to many other age-associated pathologies, the detailed mechanisms through which estrogen modulates skin repair, particularly the cell type-specific role of the two estrogen receptors, ERalpha and ERbeta, has yet to be determined. Here, we use pharmacological activation and genetic deletion to investigate the role of both ERalpha and ERbeta in cutaneous tissue repair. Unexpectedly, we report that exogenous estrogen replacement to ovariectomised mice in the absence of ERbeta actually delayed wound healing. Moreover, healing in epidermal-specific ERbeta null mice (K14-cre/ERbeta(L2/L2)) largely resembled that in global ERbeta null mice. Thus, the beneficial effects of estrogen on skin wound healing are mediated by epidermal ERbeta, in marked contrast to most other tissues in the body where ERalpha is predominant. Surprisingly, agonists to both ERalpha and ERbeta are potently antiinflammatory during skin repair, indicating clear uncoupling of inflammation and overall efficiency of repair. Thus, estrogen-mediated antiinflammatory activity is not the principal factor in accelerated wound healing.
TL;DR: The Marnaut cruise in the Sea of Marmara as discussed by the authors investigated the pore fluid chemistry of sites along the Main MarmARA Fault Zone and determined the sources and evolution of the fluids.
Abstract: As part of the 2007 Marnaut cruise in the Sea of Marmara, an investigation of the pore fluid chemistry of sites along the Main Marmara Fault zone was conducted. The goal was to define the spatial relationship between active faults and fluid outlets and to determine the sources and evolution of the fluids. Sites included basin bounding transtensional faults and strike-slip faults cutting through the topographic highs. The basin pore fluids are dominated by simple mixing of bottom water with a brackish, low-density Pleistocene Lake Marmara end-member that is advecting buoyantly and/or diffusing from a relatively shallow depth. This mix is overprinted by shallow redox reactions and carbonate precipitation. The ridge sites are more complex with evidence for deep-sourced fluids including thermogenic gas and evidence for both silicate and carbonate diagenetic processes. One site on the Western High displayed two mound structures that appear to be chemoherms atop a deep-seated fluid conduit. The fluids being expelled are brines of up to twice seawater salinity with an exotic fluid chemistry extremely high in Li, Sr, and Ba. Oil globules were observed both at the surface and in cores, and type II gas hydrates of thermogenic origin were recovered. Hydrate formation near the seafloor contributes to increase brine concentration but cannot explain their chemical composition, which appears to be influenced by diagenetic reactions at temperatures of 75°C–150°C. Hence, a potential source for fluids at this site is the water associated with the reservoir from which the gas and oil is seeping, which has been shown to be related to the Thrace Basin hydrocarbon system. Our work shows that submerged continental transform plate boundaries can be hydrologically active and exhibit a diversity of sources and processes.
TL;DR: These hybrid materials represent not only a new field of basic research where creative chemists can express themselves, but also, via their remarkable new properties and multifunctional nature, hybrids are allowing the emergence of innovative industrial applications in extremely diverse fields.
Abstract: Achieving nanostructured or hierarchical hybrid architectures involves cross-cutting synthetic strategies where all facettes of chemistry (organic, polymers, solid-state, physical, materials chemistries, biochemistry, etc..), soft matter and ingenious processing are synergistically coupled. These cross-cutting approaches are in the vein of bio-inspired synthesis strategies where the integration of different areas of expertise allows the development of complex systems of various shapes with perfect mastery at different size scales, composition, porosity, functionality, and morphology. These strategies coined "Integrative Chemistry" open a land of opportunities to create advanced hybrid materials with organic-inorganic or bio-inorganic character. These hybrid materials represent not only a new field of basic research where creative chemists can express themselves, but also, via their remarkable new properties and multifunctional nature, hybrids are allowing the emergence of innovative industrial applications in extremely diverse fields.
01 Jan 2010
Abstract: Introduction Lakes are intricately tied to the climate system in that their water level and chemistry are a manifestation of the balance between inputs (precipitation, stream inflow, surface runoff, groundwater inflow) and outputs (evaporation, stream outflow, groundwater recharge) (Mason et al ., 1994). Hence, changes in a lake's hydrologic budget caused by climatic change have the potential to alter lake level and lake chemistry. These changes, in turn, may affect the physiological responses and species composition of the lake's biota, including diatoms. Here we review the use of diatoms as indicators of hydrologic and climatic change, with an emphasis on environmental reconstruction in arid and semi-arid regions. First we discuss linkages among climate, hydrology, lake hydrochemistry, and diatoms that form the foundation for environmental reconstruction, and then we review selected examples of diatom-based studies. Lake hydrology and hydrochemistry Lakes vary in their hydrologic sensitivity to climatic change (Winter, 1990). In basins with a surface outlet, lake-level increase is constrained by topography, and any change in input is usually balanced by outflow. Thus, in open basins, lake level fluctuates relatively little, unless hydrologic change is sufficiently large to drop water level below the outlet level. In contrast, closed-basin lakes without surface outflow often show changes in level associated with changes in the balance between precipitation and evaporation (P – E).
TL;DR: The results suggest that the SufBC2D complex functions as a novel type of scaffold protein that assembles an Fe-S cluster through the mobilization of sulfur from theSufSE cysteine desulfurase and the FADH2-dependent reductive mobilization of iron.
TL;DR: A spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior is presented, which captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions.
Abstract: The human brain efficiently solves certain operations such as object recognition and categorization through a massively parallel network of dedicated processors. However, human cognition also relies on the ability to perform an arbitrarily large set of tasks by flexibly recombining different processors into a novel chain. This flexibility comes at the cost of a severe slowing down and a seriality of operations (100–500 ms per step). A limit on parallel processing is demonstrated in experimental setups such as the psychological refractory period (PRP) and the attentional blink (AB) in which the processing of an element either significantly delays (PRP) or impedes conscious access (AB) of a second, rapidly presented element. Here we present a spiking-neuron implementation of a cognitive architecture where a large number of local parallel processors assemble together to produce goal-driven behavior. The precise mapping of incoming sensory stimuli onto motor representations relies on a “router” network capable of flexibly interconnecting processors and rapidly changing its configuration from one task to another. Simulations show that, when presented with dual-task stimuli, the network exhibits parallel processing at peripheral sensory levels, a memory buffer capable of keeping the result of sensory processing on hold, and a slow serial performance at the router stage, resulting in a performance bottleneck. The network captures the detailed dynamics of human behavior during dual-task-performance, including both mean RTs and RT distributions, and establishes concrete predictions on neuronal dynamics during dual-task experiments in humans and non-human primates.
TL;DR: This review gives an overview of connexin expression in glial cells of the central nervous system, the different modes of Connexin action, including gap junctional channels and hemichannels, as well as the available methodologies to measure their activity.
TL;DR: Cluster dynamical mean field calculations based on 2-, 4-, 8-, and 16-site clusters are used to analyze the doping-driven metal insulator transition in the two-dimensional Hubbard model as discussed by the authors.
Abstract: Cluster dynamical mean-field calculations based on 2-, 4-, 8-, and 16-site clusters are used to analyze the doping-driven metal-insulator transition in the two-dimensional Hubbard model. Comparison of results obtained on different clusters enables a determination of those aspects of the physics that are common to all clusters and permits identification of artifacts associated with particular cluster geometries. A modest particle-hole asymmetry in the underlying band structure is shown to lead to qualitatively different behavior on the hole-doped side than on the electron-doped side. For particle-hole asymmetry of the sign and magnitude appropriate to high-${T}_{c}$ cuprates, the approach to the insulator from the hole-doping side is found to proceed in two stages from a high-doping region where the properties are those of a Fermi liquid with moderately renormalized parameters and very weak momentum dependence. As doping is reduced the system first enters an intermediate doping regime where the Fermi-liquid renormalizations are larger and the electron self-energy varies significantly around the Fermi surface and then passes to a small doping regime characterized by a gap on some parts of the Fermi surface but gapless behavior in other parts. On the electron-doped side the partially gapped regime does not occur, and the momentum dependence of the electron self-energy is less pronounced. Implications for the high-${T}_{c}$ cuprates and for the use of cluster dynamical mean-field methods in wider classes of problems are discussed.
TL;DR: It is confirmed that BBS1 and BBS10 are the most frequently mutated genes, followed by BBS12, and the various strategies for diagnostic mutation detection, including homozygosity mapping and targeted arrays for the detection of previously reported mutations are discussed.
Abstract: Bardet-Biedl syndrome (BBS), an emblematic disease in the rapidly evolving field of ciliopathies, is characterized by pleiotropic clinical features and extensive genetic heterogeneity. To date, 14 BBS genes have been identified, 3 of which have been found mutated only in a single BBS family each (BBS11/TRIM32, BBS13/MKS1 and BBS14/MKS4/NPHP6). Previous reports of systematic mutation detection in large cohorts of BBS families (n > 90) have dealt only with a single gene, or at most small subsets of the known BBS genes. Here we report extensive analysis of a cohort of 174 BBS families for 12/14 genes, leading to the identification of 28 novel mutations. Two pathogenic mutations in a single gene have been found in 117 families, and a single heterozygous mutation in 17 families (of which 8 involve the BBS1 recurrent mutation, M390R). We confirm that BBS1 and BBS10 are the most frequently mutated genes, followed by BBS12. No mutations have been found in BBS11/TRIM32, the identification of which as a BBS gene only relies on a single missense mutation in a single consanguineous family. While a third variant allele has been observed in a few families, they are in most cases missenses of uncertain pathogenicity, contrasting with the type of mutations observed as two alleles in a single gene. We discuss the various strategies for diagnostic mutation detection, including homozygosity mapping and targeted arrays for the detection of previously reported mutations.
TL;DR: The present review discusses recent advances that have made crucial contributions in understanding the molecular mechanisms underlying FRDA and in advancements toward potential novel therapeutic approaches.
Abstract: Friedreich’s ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. The physiopathological consequences of frataxin deficiency are a severe disruption of iron– sulfur cluster biosynthesis, mitochondrial iron overload coupled to cellular iron dysregulation and an increased sensitivity to oxidative stress. Frataxin is a highly conserved protein, which has been suggested to participate in a variety of different roles associated with cellular iron homeostasis. The present review discusses recent advances that have made crucial contributions in understanding the molecular mechanisms underlying FRDA and in advancements toward potential novel therapeutic approaches. Owing to space constraints, this review will focus on the most commonly accepted and solid molecular and biochemical studies concerning the function of frataxin and the physiopathology of the disease. We invite the reader to read the following reviews to have a more exhaustive overview of the field [Pandolfo, M. and Pastore, A. (2009) The pathogenesis of Friedreich ataxia and the structure and function of frataxin. J. Neurol., 256 (Suppl. 1), 9 – 17; Gottesfeld, J.M. (2007) Small molecules affecting transcription in Friedreich ataxia. Pharmacol. Ther., 116, 236 –2 48; Pandolfo, M. (2008) Drug insight: antioxidant therapy in inherited ataxias. Nat. Clin. Pract. Neurol., 4, 86–96; Puccio, H. (2009) Multicellular models of Friedreich ataxia. J. Neurol., 256 (Suppl. 1), 18–24].
TL;DR: It is shown that the blockade of GABAergic transmission reversed the time dependence of corticostriatal STDP, and the receptors and signalling mechanisms involved in the STDP depended on distinct coincidence detectors, which means that LTP and LTD induced by STDP at corticOSTriatal synapses are mediated by independent signalling mechanisms.
Abstract: Corticostriatal projections constitute the main input to the basal ganglia, an ensemble of interconnected subcortical nuclei involved in procedural learning Thus, long-term plasticity at corticostriatal synapses would provide a basic mechanism for the function of basal ganglia in learning and memory We had previously reported the existence of a corticostriatal anti-Hebbian spike timing-dependent plasticity (STDP) at synapses onto striatal output neurons, the medium-sized spiny neurons Here, we show that the blockade of GABAergic transmission reversed the time dependence of corticostriatal STDP We explored the receptors and signalling mechanisms involved in the corticostriatal STDP Although classical models for STDP propose NMDA receptors as the unique coincidence detector, the involvement of multiple coincidence detectors has also been demonstrated Here, we show that corticostriatal STDP depends on distinct coincidence detectors Specifically, long-term potentiation is dependent on NMDA receptor activation, while long-term depression requires distinct coincidence detectors: the phospholipase Cβ (PLCβ) and the inositol-trisphosphate receptor (IP3R)-gated calcium stores Furthermore, we found that PLCβ activation is controlled by group-I metabotropic glutamate receptors, type-1 muscarinic receptors and voltage-sensitive calcium channel activities Activation of PLCβ and IP3Rs leads to robust retrograde endocannabinoid signalling mediated by 2-arachidonoyl-glycerol and cannabinoid CB1 receptors Interestingly, the same coincidence detectors govern the corticostriatal anti-Hebbian STDP and the Hebbian STDP reported at cortical synapses Therefore, LTP and LTD induced by STDP at corticostriatal synapses are mediated by independent signalling mechanisms, each one being controlled by distinct coincidence detectors