Sensory information processing by the intraglomerular network of the olfactory bulb in mice

L’olfaction est un système sensoriel connu pour jouer un rôle essentiel dans l’intégration des signaux environnementaux. Dans le cerveau, la première étape du traitement olfactif a lieu à l'intérieur des glomérules où une variété d'interneurones reçoivent et intègrent l’information sensorielle, avant que celle-ci ne soit transmise aux neurones de projections du bulbe olfactif. Mon projet de thèse vise à mieux comprendre comment ces informations olfactives sont traitées par les interneurones glomérulaires et plus particulièrement, les interneurones glomérulaires dits "soeurs" (projetant à l'intérieur d'un même glomérule). Pour cela, j'ai utilisé un modèle de souris transgénique qui m'a permis de cibler spécifiquement les interneurones glutamatergiques du bulbe olfactif (les external tuted cells). En combinant l'imagerie structurale de haute résolution avec des enregistrements biphotoniques de l'activité calcique, j'ai pu reconstruire la morphologie dendritique de ces interneurones et étudier leur activité in vivo au sein du glomérule sur lequel ils projettent. Cette stratégie expérimentale particulière m'a permis de mettre en évidence pour la première fois l'émergence de cartes d'activités cellulaires dynamiques, à l'intérieur des glomérules, qui sont spécifiques de l'identité et de la concentration des odeurs perçues. La découverte de ce nouveau mécanisme cellulaire pourrait montrer une étape importante de décorrélation des entrées sensorielles qui proviennent de la périphérie et, ouvrir la voie vers la caractérisation complète d'un nouveau modèle de codage des informations sensorielles dans le bulbe olfactif.Olfaction is a sensory system known to play an essential role in the integration of environmental signals. In the brain, the first step of olfactory processing takes place within the glomeruli where a variety of interneurons receive and integrate sensory information, before it is transmitted to olfactory bulb output neurons. My PhD project aims to better understand how olfactory information is processed by glomerular interneurons and more particularly, the so-called "sister" glomerular interneurons (projecting within the same glomerulus). In the following work, I used a transgenic mouse model that allowed me to specifically target the glutamatergic interneurons of the olfactory bulb (the external tuted cells). By combining high resolution structural imaging with two-photon in vivo calcium activity, I was able to reconstruct the dendritic morphology of these interneurons and study their activity in vivo within the glomerulus on which they project. This experimental strategy, not commonly used in olfaction, allowed me to demonstrate for the first time the emergence of dynamic cellular activity maps within glomeruli that are specific to odor identity and concentration. The discovery of this new cellular mechanism could show an important step in the decorrelation of sensory inputs from the periphery and pave the way for a new model of sensory information coding in the olfactory bulb

Recent and present sedimentary fluxes of heavy metals and radionuclides in oligotrophic Lake Annecy, France

The present study focuses on two aspects of heavy metals and radionuclide fluxes to lake Annecy: a long term, secular evolution by analysing dated sediment cores, and a short term, seasonal evolution through the analysis of settling particles collected by sediment traps. Compared to background values prior to 1900, sediment cores reveal a two-fold (Cd, Cu, Zn) to a four-fold (Pb) increase in heavy metal concentration after the 40s, and a smaller decrease after the 70s except for Cu, which does not decrease. Sediment traps moored from April 1998 to November 2000 record strong variations of particles (range: 0.5-6.1 g m$^{-2}$ d$^{-1}$), organic matter (range 0.03-0.27 g m$^{-2}$ d$^{-1}$) and carbonate fluxes (range: 0.2-4.9 g m$^{-2}$ d$^{-1}$). The maximum fluxes are observed at the end of spring and summer, related to increased phytoplankton production. Mean annual heavy metal fluxes (0.014 $\mu$g$\cdot$cm$^{-2}\cdot$y$^{-1}$ for Cd, 1 $\mu$g$\cdot$cm$^{-2}\cdot$y$^{-1}$ for Pb and Cu and 2.8 $\mu$g$\cdot$cm$^{-2}\cdot$y$^{-1}$ for Zn) are lower than those recorded in the surface layers of the sediment cores. No relation has been observed between fluxes of heavy metal and of particles. Comparison of heavy metal fluxes in Lake Annecy with two other peri-alpine lakes show that this lake receive more Cu and Pb of anthropogenic origin, in spite of the sewage collector built around the lake

Recent and present sedimentary fluxes of heavy metals and radionuclides in oligotrophic Lake Annecy, France

The present study focuses on two aspects of heavy metals and radionuclide fluxes to lake Annecy: a long term. secular evolution by analysing dated sediment cores, and a short term, seasonal evolution through the analysis of settling particles collected by sediment traps. Compared to background values prior to 1900, sediment cores reveal a two-fold (Cd, Cu, Zn) to a four-fold (Pb) increase in heavy metal concentration after the 40s, and a smaller decrease after the 70s except for Cu, which does not decrease. Sediment traps moored from April 1998 to November 2000 record strong variations of particles (range: 0.5 - 6.1 g m(-2) d(-1)), organic matter (range 0.03 - 0.27 g m(-2) d(-1)) and carbonate fluxes (range: 0.2 - 4.9 g m(-2) d(-1)). The maximum fluxes are observed at the end of spring and summer, related to increased phytoplankton production. Mean annual heavy metal fluxes (0.014 mug.cm(-2).y(-1) for Cd, 1 mug.cm(-2). y(-1) for Ph and Cu and 2.8 mug.cm(-2).y(-1) for Zn) are lower than those recorded in the surface layers of the sediment cores. No relation has been observed between fluxes of heavy metal and of particles. Comparison of heavy metal fluxes in Lake Annecy with two other peri-alpine lakes show that this lake receive more Cu and Ph of anthropogenic origin, in spite of the sewage collector built around the lake

Effects of sensory deprivation on glomerular interneurons in the mouse olfactory bulb: differences in mortality and phenotypic adjustment of dopaminergic neurons

International audienceNeurogenesis persists in the mammalian subventricular zone after birth, producing various populations of olfactory bulb (OB) interneurons, including GABAergic and mixed dopaminergic/GABAergic (DA) neurons for the glomerular layer. While olfactory sensory activity is a major factor controlling the integration of new neurons, its impact on specific subtypes is not well understood. In this study we used genetic labeling of defined neuron subsets, in combination with reversible unilateral sensory deprivation and longitudinal in vivo imaging, to examine the behavior of postnatally born glomerular neurons. We find that a small fraction of GABAergic and of DA neurons die after 4 weeks of sensory deprivation while surviving DA-neurons exhibit a substantial decrease in tyrosine hydroxylase (TH) expression levels. Importantly, after reopening of the naris, cell death is arrested and TH levels go back to normal levels, indicating a specific adaptation to the level of sensory activity. We conclude that sensory deprivation induces adjustments in the population of glomerular neurons, involving both, cell death and adaptation of neurotransmitter use in specific neuron types. Our study highlights the dynamic nature of glomerular neurons in response to sensory deprivation and provide valuable insights into the plasticity and adaptability of the olfactory system

Arsenic in Lake Geneva (Switzerland, France): long term monitoring, and redox and methylation speciation in an As unpolluted, oligo-mesotrophic lake

Arsenic speciation was followed monthly along the spring productivity period (January–June 2021) in the Petit Lac (76 m deep) and in April and June 2021 in the Grand Lac (309.7 m deep) of Lake Geneva (Switzerland/France). Lake Geneva is presently an oligo-mesotrophic lake, and As-unpolluted. The water column never becomes anoxic but the oxygen saturation at the bottom of the Grand Lac is now below 30% owing to lack of water column mixing since 2012. Thus, this lake offers excellent conditions to study As behaviour in an unpolluted, oxic freshwater body. The following ‘dissolved’ As species: iAs(III), iAs(III + V), MA(III), MA(III + V), DMA(III + V), and TMAO were analysed by HG-CT-ICP-MS/MS. Water column measurements were complemented with occasional sampling in the main rivers feeding the lake and in the interstitial waters of a sediment core. The presence of MA(III) and TMAO and the predominance of iAs(V) in lake and river samples has been confirmed as well as the key role of algae in the formation of organic species. While the total ‘dissolved’ As concentrations showed nearly vertical profiles in the Petit Lac, As concentrations steadily increase at deeper depths in the Grand Lac due to the lack of mixing and build up in bottom waters. The evaluation of 25 years of monthly data of ‘dissolved’ As concentrations showed no significant temporal trends between 1997 and 2021. The observed seasonal character of the ‘dissolved’ As along this period coincides with a lack of seasonality in As mass inventories, pointing to a seasonal internal cycling of As species in the water column with exchanges between the ‘dissolved’ and ‘particulate’ (i.e., algae) fractions.Peer reviewe

Fluorescence Study of Lipid-based DNA Carriers Properties: Influence of Cationic Lipid Chemical Structure

International audienceWe report here a study on the physicochemical properties of cationic phospholipids liposomes used for lipoplex formulation and DNA transfer. The original cationic phospholipids synthesized in our laboratory are first presented with the liposome formulation process. The second part deals with the liposomes fusogenic properties studied by fluorescence resonant energy transfer (FRET). The nature of the cationic polar head and the formulation with or without a neutral colipid have a great influence on the FRET signal. The third part reports the study of the viscosity of the liposome by fluorescence anisotropy measurements. It has been observed that the vectors having a saturated lipid chain exhibit a more pronounced anisotropy than those having unsaturated lipid chains. Finally, liposomes formed by a mixture of phospholipids and DC-Chol (a rigid lipid) leads to increase the anisotropy denoting a more rigid liposome

Physicochemical properties of cationic lipophosphoramidates with an arsonium head group and various lipid chains: A structure–activity approach

International audienceWe studied the physicochemical properties of some cationic lipophosphoramidates used as gene vectors in an attempt to better understand the link between the nature of the hydrophobic chain and both physico-chemical properties and transfection efficiency. These compounds have an arsonium head group and various chain lengths and unsaturation numbers. The synthesis of cationic phospholipids with oleic (Guenin et al., 2000 [1]; Floch et al., 2000 [2]) or linoleic (Fraix et al., 2011 [3]; Le Gall et al., 2010 [4]) chains has already been reported by our group and their efficiency as gene carriers has been demonstrated. Four new compounds were synthesized which incorporated either C14:0, C18:0, C20:4 or C20:5 chains. The membrane fluidity was studied by fluorescence anisotropy measurements. The fusion of liposomes and lipoplexes with membrane models was studied by Förster Resonant Energy Transfer. Finally, DNA condensation was studied and the lipoplexes were tested in vitro to quantify their transfection efficiency. From the results obtained on these cationic lipophosphoramidates series, we show that aliphatic chain length and unsaturation number have an important influence on liposomes physicochemical properties and transfection efficiency. However there is no direct link between fluidity and fusion efficiency or between fluidity and DNA condensation. Nevertheless, it seems that for best transfection efficiency the compounds need to combine the properties of fluidity, fusion efficiency and DNA condensation efficiency. This was the case for the C18:1 and C18:2 compounds

Effects of a Novel Archaeal Tetraether-based Colipid on the In Vivo Gene Transfer Activity of Two Cationic Amphiphiles

International audienceGene therapy for treating inherited diseases like cystic fibrosis might be achieved using multi-modular non-viral lipid-based systems. To date, most optimizations have concerned cationic lipids rather than colipids. In this study, an original archaeal tetraether derivative was used as a colipid in combination with one or the other of two monocationic amphiphiles. The liposomes obtained, termed archaeosomes, were characterized regarding lipid self-assembling properties, macroscopic/microscopic structures, DNA condensation/neutralization/relaxation abilities, and colloidal stability in presence of serum. In addition, gene transfer experiments were conducted in mice with lipid/DNA complexes being administered via systemic or local delivery routes. Altogether, the results showed that the tetraether colipid can provide complexes with different in vivo transfection abilities depending on the lipid combination, the lipid/colipid molar ratio, and the administration route. This original colipid appears thus as an innovative modular platform endowed with properties possibly beneficial for fine-tuning of in vivo lipofection and other biomedical applications