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

New 3-hit model of schizophrenia: behavioral and electrophysiological investigations

International audienc

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

International audienc

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

Patrimoines de la Seconde Guerre mondiale en Normandie

Ce projet collectif de recherche lancé en 2015 vise à inventorier dans les départements du Calvados, de la Manche et de l’Orne tous les éléments du dernier conflit qui sont conservés, disparus ou enfouis, et à en restituer la cohérence historique. Il vise particulièrement à étudier les différents éléments dans l’histoire du conflit et leur place dans les dispositifs militaires. Il porte donc aussi bien sur les vestiges liés à l’Occupation que sur les vestiges alliés ou les traces et aménageme..

Vestiges de la Seconde Guerre mondiale en Basse-Normandie

Ce programme collectif de recherche vise à inventorier de manière exhaustive les éléments conservés, disparus ou enfouis, formant des ensembles cohérents, sans se limiter aux seules élévations, et à appréhender les différents éléments dans l’histoire du conflit et leur place dans le dispositif défensif. Il s’appuie à la fois sur des études documentaires, des recherches de terrain ainsi que sur une base de données couplée à un SIG. Ce projet répond à un besoin urgent de gestion de ce patrimoin..

Vestiges de la Seconde Guerre mondiale en Basse-Normandie

Pour rappel, ce programme collectif de recherche vise à inventorier de manière exhaustive les éléments conservés, disparus ou enfouis, formant des ensembles cohérents, sans se limiter aux seules élévations, et à appréhender les différents éléments dans l’histoire du conflit et leur place dans le dispositif défensif. Il s’appuie à la fois sur des études documentaires, des recherches de terrain ainsi qu’une base de données couplée à un SIG. Ce projet répond à un besoin urgent de gestion de ce p..

In Situ Microscopy Analysis Reveals Local Innate Immune Response Developed around Brucella Infected Cells in Resistant and Susceptible Mice

Brucella are facultative intracellular bacteria that chronically infect humans and animals causing brucellosis. Brucella are able to invade and replicate in a broad range of cell lines in vitro, however the cells supporting bacterial growth in vivo are largely unknown. In order to identify these, we used a Brucella melitensis strain stably expressing mCherry fluorescent protein to determine the phenotype of infected cells in spleen and liver, two major sites of B. melitensis growth in mice. In both tissues, the majority of primary infected cells expressed the F4/80 myeloid marker. The peak of infection correlated with granuloma development. These structures were mainly composed of CD11b+ F4/80+ MHC-II+ cells expressing iNOS/NOS2 enzyme. A fraction of these cells also expressed CD11c marker and appeared similar to inflammatory dendritic cells (DCs). Analysis of genetically deficient mice revealed that differentiation of iNOS+ inflammatory DC, granuloma formation and control of bacterial growth were deeply affected by the absence of MyD88, IL-12p35 and IFN-γ molecules. During chronic phase of infection in susceptible mice, we identified a particular subset of DC expressing both CD11c and CD205, serving as a reservoir for the bacteria. Taken together, our results describe the cellular nature of immune effectors involved during Brucella infection and reveal a previously unappreciated role for DC subsets, both as effectors and reservoir cells, in the pathogenesis of brucellosis

Brain Phenotype of Transgenic Mice Overexpressing Cystathionine β-Synthase

The cystathionine β-synthase (CBS) gene, located on human chromosome 21q22.3, is a good candidate for playing a role in the Down Syndrome (DS) cognitive profile: it is overexpressed in the brain of individuals with DS, and it encodes a key enzyme of sulfur-containing amino acid (SAA) metabolism, a pathway important for several brain physiological processes.Here, we have studied the neural consequences of CBS overexpression in a transgenic mouse line (60.4P102D1) expressing the human CBS gene under the control of its endogenous regulatory regions. These mice displayed a ∼2-fold increase in total CBS proteins in different brain areas and a ∼1.3-fold increase in CBS activity in the cerebellum and the hippocampus. No major disturbance of SAA metabolism was observed, and the transgenic mice showed normal behavior in the rotarod and passive avoidance tests. However, we found that hippocampal synaptic plasticity is facilitated in the 60.4P102D1 line.We demonstrate that CBS overexpression has functional consequences on hippocampal neuronal networks. These results shed new light on the function of the CBS gene, and raise the interesting possibility that CBS overexpression might have an advantageous effect on some cognitive functions in DS