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Area CA2 is a critical region for diverse hippocampal functions including social recognition memory. This region has unique properties and connectivity. Notably, intra-hippocampal excitatory inputs to CA2 lack canonical long-term plasticity, but inhibitory transmission expresses a long-term depression mediated by Delta-opioid receptors (DOR-iLTDs). Evidence indicates that DOR-iLTDs are insufficient to underlie social coding. Here, we report a novel inhibitory plasticity mediated by cannabinoid type 1 receptor activation (CB1R-iLTD). Surprisingly, CB1R-iLTD requires previous induction of DOR-iLTDs, indicating a permissive role for DOR plasticity. Blockade of CB1Rs in CA2 completely prevents social memory formation. Furthermore, the sequentiality of DOR- and CB1R-mediated plasticity occurs in vivo during successive social interactions. Finally, CB1R-iLTD is altered in a mouse model of schizophrenia with impaired social cognition but is rescued by a manipulation that also rescues social memory. Altogether, our data reveal a unique interplay between two inhibitory plasticities and a novel mechanism for social memory formation.

International audience; Parvalbumin (PV)-expressing interneurons which are often associated with the specific extracellular matrix perineuronal net (PNN) play a critical role in the alteration of brain activity and memory performance in Alzheimer's disease (AD). The integrity of these neurons is crucial for normal functioning of the hippocampal subfield CA2, and hence, social memory formation. Here, we find that social memory deficits of mouse models of AD are associated with decreased presence of PNN around PV cells and long-term synaptic plasticity in area CA2. Furthermore, single local injection of the growth factor neuregulin-1 (NRG1) is sufficient to restore both PV/PNN levels and social memory performance of these mice. Thus, the PV/PNN disruption in area CA2 could play a causal role in social memory deficits of AD mice, and activating PV cell pro-maturation pathways may be sufficient to restore social memory.

Able to monitor very precisely CO2 gases concentration in the atmosphere (better than 1 ppm), MicroCarb is a CNES mission which instrument is a passive Short Wave InfraRed spectrometer that will help scientists to better understand the planet’s major ecosystems and gain a clearer picture of its carbon budget at regional scales. Reaching such a monitoring precision means that the instrument has very stringent requirements especially in terms of radiometry, spectral filtering, spectral bands co-registration and polarization sensitivity. The MicroCarb instrument is currently under integration at Airbus Defence and Space facilities in Toulouse (France). It is based on an innovative concept permitting the acquisition of the spectral bands using a single split-pupil telescope, spectrometer and detector. Spectral bands multiplexing is obtained by the grating, each band corresponding to a different diffraction order, between 15 and 40. The split-pupil concept is characterized by 3 sets of 4 to 5 assembled prisms at entrance telescope pupil, spectrometer slit and in front of the detector, all participating to the complex spectral filtering. All the components considered as critical for the performances of the instrument have been manufactured and are under integration: the echelle grating replicated in a SiC substrate, the assembled optical elements with narrow spectral filtering coatings and the Dual Babinet polarization scrambler. In this paper we will focus on these optical components, detailing for each one how the stringent requirements of the instrument have been transposed to their specification, close to the limits of manufacturability. We will be able to present their development and achievement with respect to these specifications and how they impact the global performances of the instrument.

Group III metabotropic glutamate (mGlu) receptors modulate glutamatergic and GABAergic transmission in the basal ganglia. In this study, we examined a novel orthosteric agonist at the mGlu4 receptor, LSP1-2111, for its ability to affect L-DOPA-induced dyskinesia (LID), in a mouse model. In 6-OHDA-lesioned mice treated with L-DOPA, chronic co- administration of LSP1-2111 significantly attenuated the development of abnormal involuntary movements, which are regarded as a marker of dyskinesia. In contrast, a single injection of LSP1-2111 did not modify the expression of LID, once this condition had been established by previous administration of L-DOPA. LSP1-2111 did not affect L-DOPA-induced cAMP and extracellular signal-regulated protein kinase signaling, which have been previoulsy implicated in dyskinesia. These results indicate that co-administration of LSP1-2111 may improve the efficacy of standard L-DOPA therapy by attenuating its liability for dyskinesia.

International audience; Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, >500, 0.34 microM at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/microL, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.

Cadmium is very toxic at low concentrations, but the basis for its toxicity is not clearly understood. We analyzed the proteomic response of yeast cells to acute cadmium stress and identified 54 induced and 43 repressed proteins. A striking result is the strong induction of 9 enzymes of the sulfur amino acid biosynthetic pathway. Accordingly, we observed that glutathione synthesis is strongly increased in response to cadmium treatment. Several proteins with antioxidant properties were also induced. The induction of nine proteins is dependent upon the transactivator Yap1p, consistent with the cadmium hypersensitive phenotype of the YAP1-disrupted strain. Most of these proteins are also overexpressed in a strain overexpressing Yap1p, a result that correlates with the cadmium hyper-resistant phenotype of this strain. Two of these Yap1p-dependent proteins, thioredoxin and thioredoxin reductase, play an important role in cadmium tolerance because strains lacking the corresponding genes are hypersensitive to this metal. Altogether, our data indicate that the two cellular thiol redox systems, glutathione and thioredoxin, are essential for cellular defense against cadmium.

The adhesion between metals and polymers has attracted much interest in recent years due to the increasing use of metal/polymer assemblies, for example, in the fields of packaging, architecture, and automotive manufacturing. Among the parameters controlling the adhesion properties of metal/polymer systems, the acid-base properties of both materials appear to play an important role. Two methods are proposed for assessing and quantifying the acido-basicity of passive films on metals: X-ray photoelectron spectroscopy (XPS and X-ray absorption near edge structure (XANES). These techniques were used here to characterize the acid-base properties of a large set of passivated aluminum surfaces. Both XPS-monitored Fermi level shift and XANES formic acid and pyridine adsorption measurements were found in good agreement in the establishment of a relative basicity scale for the studied surfaces. Moreover, the results were cross-va idate with those of the novel photoelectrochemical approach to the acid-base properties of aluminum surfaces presented in Part I.

The acid-base properties of aluminum surfaces have recently attracted much interest due to their consequences on the adhesion of organic coatings. The present work deals with a novel photoelectrochemical approach to the acid-base properties of aluminum surfaces. Passive films were considered here as wide-gap semiconductors. When they are in contact with an electrolyte, a space charge builds up. A negative (positive) space charge is considered here as a sign of an electron donor (acceptor) surface, i.e., to a Lewis basic (acid) surface. The more negative (positive) the space charge or the corresponding band bending in the semiconductor, the more basic (acid) the passivated surface. The spectrophotoelectrochemical response of the samples polarized at the rest potential under ultraviolet illumination allowed the measurement of the band bending as the difference between the thresholds of two photoemission phenomena from the Fermi level toward the passive film conduction band at the inner and outer interfaces of the passive films. Negative band bendings were always obtained, evidencing the basic character of the analyzed surfaces. A basicity scale was obtained which is compared in Part II to that deduced from X-ray photoelectron and X-ray absorption near-edge structure studies.

The existence of β-C 3 N 4 with hardness characteristics similar or better than diamond was predicted in 1990 by Liu and Cohen. Many studies have since been devoted to the synthesis of this compound. In the present work, carbon nitride films were deposited by various reactive magnetron sputtering processes of graphite targets in pure nitrogen and characterized by AES, XPS, x-ray adsorption near-edge structure (XANES) and static time-of-flight SIMS (ToF-SIMS). Various bonding states (single and double bond) are observed between carbon and nitrogen atoms and between carbon atoms but there is no evidence in the XANES results for either the presence of carbon-nitrogen triple bonds or a pyridine-like ring structure. Surface N/C ratios were estimated to be close to 0.3. Carbon K-edge XANES lineshapes, the C 1s plasmon-loss structure and the calculated density (2.2 g cm -3 ) indicate that the films are similar to diamond-like carbon without long-range ordering. The presence of C x N y fragments with 1 ≤ y < 4 and the low abundance of CH x and CH x N y fragments in ToF-SIMS spectra further confirm that the carbon atoms do not adopt a graphite or pyridine-like cyclic two-dimensional structure and that the films are not significantly hydrogenated. A three-phase solid solution model is proposed for the composition of the films: a 'free' carbon phase, an sp 3 -carbon-nitrided phase and an sp 2 -carbon-nitrided phase. The relative proportion of these phases is influenced by the deposition conditions. Enhanced plasma ionization reactive magnetron sputtering leads to higher density and to a higher fraction of the sp 3 carbon phase.

Hard coatings are commonly used today to enhance the life of numerous tools and wear parts. As carbon nitride and TiN/NbN superlattice films prepared by reactive sputtering were being evaluated for such tribological applications, it appeared necessary to test their thermal behavior to determine their stability at high temperatures. The coatings were reactively sputtered on silicon, M1 steel, or cemented carbide substrates. Two deposition conditions were used for the carbon nitride films producing either soft or hard films. The effect of a metal interlayer, either chromium or titanium, has also been studied. Two modulation periods were used for the TiN/NbN films with the same deposition conditions. Thermal annealings were performed up to 700 °C under vacuum in the 10−6 Torr range. Several properties of the coatings before and after these annealings were evaluated and compared, including hardness (nano‐indentation), adhesion/cohesion (scratch test), structure x‐ray diffraction, and composition Auger electron spectroscopy. The carbon nitride coatings lost part of their nitrogen, and both the hardness and the critical load dropped as the annealing temperature was increased. Carbon nitride films deposited on silicon wafers peeled off after treatment at 400 °C, while films deposited on an M1 steel remained adhered. A critical temperature for both chemical and physical properties around 600 °C was observed. For the TiN/NbN superlattice films, annealing up to 700 °C caused almost no intermixing, while the nitrogen content, the hardness, the adhesion/cohesion, and the structure remained unaffected.

International audience; Disruption of gene flow among demes after landscape fragmentation can facilitate local adaptation but increase the effect of genetic drift and inbreeding. The joint effects of these conflicting forces on the mean fitness of individuals in a population are unknown. Through simulations, we explored the effect of increased isolation on the evolution of genetic load over the short and long term when fitness depends in part on local adaptation. We ignored genetic effects on demography. We modeled complex genomes, where a subset of the loci were under divergent selection in different localities. When a fraction of the loci were under heterogeneous selection, isolation increased mean fitness in larger demes made up of hundreds of individuals because of improved local adaptation. In smaller demes of tens of individuals, increased isolation improved local adaptation very little and reduced overall fitness. Short-term improvement of mean fitness after fragmentation may not be indicative of the long-term evolution of fitness. Whatever the deme size and potential for local adaptation, migration of one or two individuals per generation minimized the genetic load in general. The slow dynamics of mean fitness following fragmentation suggests that conservation measures should be implemented before the consequences of isolation on the genetic load become of concern.

Yeasts lacking cytoplasmic superoxide dismutase (Cu,Zn-SOD) activity are permanently subjected to oxidative stress. We used two-dimensional PAGE to examine the proteome pattern of Saccharomyces cerevisiae strains lacking Cu,Zn-SOD. We found a new stable form of alkyl hydroperoxide reductase 1 (Ahp1) with a lower isoelectric point. This form was also present in wild type strains after treatment with tert-butyl hydroperoxide. In vitro enzyme assays showed that Ahp1p had lower specific activity in strains lacking Cu,Zn-SOD. We studied three mutants presenting a reduced production of the low pI variant under oxidative stress conditions. Two of the mutants (C62S and S59D) were totally inactive, thus suggesting that the acidic form of Ahp1p may only appear when the enzyme is functional. The other mutant (S59A) was active in vitro and was more resistant to inactivation by tert-butyl hydroperoxide than the wild type enzyme. Furthermore, the inactivation of Ahp1p in vitro is correlated with its conversion to the low pI form. These results suggest that in vivo during some particular oxidative stress (alkyl hydroperoxide treatment or lack of Cu,Zn-SOD activity but not hydrogen peroxide treatment), the catalytic cysteine of Ahp1p is more oxidized than cysteine-sulfenic acid (a natural occurring intermediate of the enzymatic reaction) and that cysteine-sulfinic acid or cysteine-sulfonic acid variant may be inactive.