Long-Term Depression in the Hippocampal CA1 Area of Aged Rats, Revisited: Contribution of Temporal Constraints Related to Slice Preparation

BACKGROUND: The effects of low-frequency conditioning stimulation (LFS, 900 pulses at 1 Hz) of glutamatergic afferents in CA1 hippocampal area using slices from two different strains of adult (3-5 month-old) and aged (23-27 month-old) rats were reinvestigated regarding the discrepancies in the literature concerning the expression of long-term depression (LTD) in the aging brain. METHODOLOGY/PRINCIPAL FINDINGS: N-methyl-D-aspartate receptor (NMDA-R) dependent LTD was examined in both adult (n = 21) and aged (n = 22) Sprague-Dawley rats. While equivalent amounts of LTD could be obtained in both ages, there was significant variability depending upon the time between the slices were made and when they were tested. LTD was not apparent if slices were tested within 3 hours of dissection. The amount of LTD increased over the next three hours but more in adult than in aged rats. This age-related impairment was abolished by exogenous d-serine, thus reflecting the reduced activation of the NMDA-R glycine-binding site by the endogenous agonist in aged rats. Then, the amount of LTD reached asymptote at 5-7 hours following dissection. Similar temporal profiles of LTD expression were seen in young and aged Wistar rats. CONCLUSIONS/SIGNIFICANCE: Taken together, these results sound a cautionary note regarding the existence of an experimental "window of opportunity" for studying the effects of aging on LTD expression in hippocampal slice preparation

Micromegas detector developments for MIMAC

The aim of the MIMAC project is to detect non-baryonic Dark Matter with a directional TPC. The recent Micromegas efforts towards building a large size detector will be described, in particular the characterization measurements of a prototype detector of 10 $\times$ 10 cm$^2$ with a 2 dimensional readout plane. Track reconstruction with alpha particles will be shown.Comment: 8 pages, 7 figures Proceedings of the 3rd International conference on Directional Detection of Dark Matter (CYGNUS 2011), Aussois, France, 8-10 June 2011; corrections on author affiliation

D-SERINE CONTRIBUTES TO β-AMYLOID-DEPENDENT PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

International audienceB fEPSP/PFV ra>o 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 WT 5xFAD 5xFAD/SR-/-+ D-s e ri n e + D-s e ri n e + D-s e ri n e Key regulators of the structural and funcFonal brain plasFcity, the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) requires the binding of the co-agonist D-serine to be acFvated. In Alzheimer's disease (AD), soluble oligomers of the beta-amyloid pepFde (Aßo) affect NMDARs possibly through mechanisms involving changes in D-serine levels since Aßo sFmulate in vitro the producFon of the co-agonist. In this study, we asked whether D-serine contributes in vivo to morpho-funcFonal NMDAR-related deregulaFons mediated by Aßo. Behavioral analysis combined to electrophysiological recordings at CA1/CA3 hippocampal synapses have been thus conducted in the 5xFAD transgenic mice model of amyloïdogenesis displaying marked increase in Aßo rates and compared to 5xFAD animals in which the homozygous gene of the serine racemase (SR) that synthesizes D-serine, has been jointly invalidated. Our results therefore show that deleFon of serine racemase prevents memory-related behavioral deficits observed in mice with prominent features of amyloidogenesis as well as impairment of NMDAR-dependent funcFonal plasFcity, suggesFng a significant contribuFon of D-serine in NMDAR-dependent β-amyloid-related pathophysiology of Alzheimer's disease. EXPERIMENTAL PROCEDURES 1) Behavioral analysis: 8-min spontaneous alternaFon test was performed in a Y maze apparatus to assess working memory performances in 10-12 months of aged mice. Successive entry of the three arms of the maze was considered as an alternaFon. The percentage of alternaFon was calculated as follows: number of alternaFons / (total number of arms visited-2) x 100. 2) Electrophysiology: Hippocampal slices (400 µm thickness) were cut from two groups of WT, 5xFAD/SR +/+ and 5xFAD/SR-/-mice aged 3-4 or 10-12 months. Field excitatory postsynapFc potenFals (fEPSPs) and presynapFc fiber volley (PFV) were extracellularly recorded in CA1 stratum radiatum aner electrical sFmulaFon of Schaffer collaterals. Input/output curves of the fEPSP/PFV raFo of isolated NMDAr-mediated fEPSPs were constructed in a low magnesium medium supplemented with the non-NMDAr antagonist NBQX (10µM) before and 15 min aner addiFon of D-serine (100 µM). High frequency (HFS)-induced long-term potenFaFon (LTP) was studied in control medium aner tetanic sFmulaFon consisFng in one train at 100 Hz delivered for 1 sec. TesFng sFmulaFon was then resumed for 60 min aner HFS. 3) Semi-quanFtaFve immunoblopng analysis: Hippocampal Fssue was homogenized in protein lysis buffer. The membranes were probed with anFbodiesaginst GluN1 (1:750

Probing neutralino dark matter in the MSSM & the NMSSM with directional detection

We investigate the capability of directional detectors to probe neutralino dark matter in the Minimal Supersymmetric Standard Model and the Next-to-Minimal Supersymmetric Standard Model with parameters defined at the weak scale. We show that directional detectors such as the future MIMAC detector will probe spin dependent dark matter scattering on nucleons that are beyond the reach of current spin independent detectors. The complementarity between indirect searches, in particular using gamma rays from dwarf spheroidal galaxies, spin dependent and spin independent direct search techniques is emphasized. We comment on the impact of the negative results on squark searches at the LHC. Finally, we investigate how the fundamental parameters of the models can be constrained in the event of a dark matter signal.Comment: 21 pages, 16 figure

IMPACT OF D-SERINE DEPLETION IN THE β-AMYLOID CASCADERELATED TO ALZHEIMER’S DISEASE

International audienceD-serine, as a co-agonist of N-methyl-D-aspartate subtype of glutamate receptors (NMDAR), is a key regulator of their activation and hence involves in functional brain plasticity and memory process. The homeostasis of these receptors is affected by soluble oligomers of the beta-amyloid peptide (Aß) in Alzheimer´s disease (AD). In the course of AD, early functional dysregulations of NMDAR are well known, even though contribution of D-serine remains so far to be determined. In 3-4 month-old transgenic mice model of amyloïdogenesis (5xFAD) showing marked increase in Aß rates and apparent unaffected D-serine levels, extracellular electrophysiological recordings reveal impaired NMDAR-dependent long-term potentiation at CA1/CA3 hippocampal synapses, without significant changes in basal synaptic transmission. This deficit persists at 12 month of age when amyloid deposits are present with concomitant disabilities in cognitive functions. Generating 5xFAD mice with depletion of D-serine (through invalidation of the synthesis enzyme: Serine Racemase), we observed that these functional alterations and the long-term behavioral impairment were prevented whereas Aßo rates remain significantly elevated and comparable to 5xAFD mice. Therefore, these results provide convincing evidence for a critical and transient involvement of D-serine in hippocampal network dysfunctions and related cognitive disabilities driven by increased amyloidogenesis

Altering glutamate transmission in combination with an early post-natal stress to mimic schizophrenia in male and female mice

International audienc

D-­‐SERINE IS INVOLVED IN THE β-­‐AMYLOID-­‐RELATED PATHOPHYSIOLOGYIN ALZHEIMER’S DISEASE

International audienc

Low energy electron/recoil discrimination for directional Dark Matter detection

Directional detection is a promising Dark Matter search strategy. Even though it could accommodate to a sizeable background contamination, electron/recoil discrimination remains a key and challenging issue as for direction-insensitive detectors. The measurement of the 3D track may be used to discriminate electrons from nuclear recoils. While a high rejection power is expected above 20 keV ionization, a dedicated data analysis is needed at low energy. After identifying discriminant observables, a multivariate analysis, namely a Boosted Decision Tree, is proposed, enabling an efficient event tagging for Dark Matter search. We show that it allows us to optimize rejection while keeping a rather high efficiency which is compulsory for rare event search.With respect to a sequential analysis, the rejection is about 20 times higher with a multivariate analysis, for the same Dark Matter exclusion limit.Comment: 20 pages, 20 figure

Iterative rigid body transformation estimation for visual 3-D object tracking

We present a novel yet simple 3D stereo vision tracking algorithm which computes the position and orientation of an object from the location of markers attached to the object. The novelty of this algorithm is that it does not assume that the markers are tracked synchronously. This provides a higher robustness to the noise in the data, missing points and outliers. The principle of the algorithm is to perform a simple gradient descent on the rigid body transformation describing the object position and orientation. This is proved to converge to the correct solution and is illustrated in a simple experimental setup involving two USB cameras