Hypothalamus plays a critical role in both the monitoring and the regulation of energy needs. Energy stores are monitored by the hypothalamus using metabolic and neural signals from the periphery. These signals trigger neuroendocrine, autonomic and behavioral responses, maintaining energy homeostasis. Hypothalamic neurons responding to glucose levels have been identified, but the process allowing the transfer of blood glucose to these hypothalamic sensitive neurons remains unclear. Glucose sensing implies the glucose inhibited (GI) or glucose excited (GE) neurons. GE neurons respond to increased glucose concentration and are mainly found in the arcuate nucleus. The mechanisms underlying glucose responsiveness of these neurons share similarities with pancreatic beta-cells. One of these shared mechanisms is the redox signaling through mitochondrial reactive oxygen species (mROS) production when glucose rises, especially through the conversion of the superoxide anions production into H2O2. Moreover, evidence shows that in the hypothalamus glucose responsiveness implies two populations of cells, i.e. the GE neurons themselves and upstream, the astrocytes which appear absolutely required. Indeed, studies have highlighted that the entire effect of glucose requires its conversion to lactate, which is performed by astrocytes. However, whether important studies have highlighted this metabolic coupling mechanism between the two populations, any of them have focus on upstream actors that allow the final supply of lactate to GE neurons. This early step in providing the information of the circulating glycemic level to GE neurons might be of prime importance to ensure a right transduction of the metabolic status of the body to the hypothalamus. Astrocytes are a physical link between vasculature and neurons through their perivascular endfeet. Moreover, perivascular astrocytes have a high level of connexin (Cx) expression. Cxs are the gap junction channel-forming proteins and allow direct intercellular communication as these channels are permeable to small signaling molecules. In astrocytes they constitute the morphological support for astroglial networks. These networks ensure an intercellular pathway between gliovascular interface and the neuronal energy demand. Recently, using fluorescent glucose derivatives it was reported that astroglial metabolic networks are regulated by neuronal activity in the hippocampus. In addition, in absence of external glucose, the trafficking of lactate through astroglial networks was sufficient to maintained synaptic activity. These findings highlights that gap-junctions mediated metabolic networks contribute to the delivery of energetic substrates to neurons. In the case of GE neurons, the connectivity through connexins of the astrocytic network, allowing the intercellular trafficking of glucose and its metabolites, might take a crucial importance. Another interesting feature of this astrocytic network is its sensitivity to superoxide anions through H2O2 derivative. The requirement of increased mROS for adequate responses of GE neurons to glucose rises and the H2O2-induced increased permeability of gap-junctions mediated metabolic network suggest that a redox regulated interplay between de two cell populations might exist. Implication of astrocytes through the release of lactate in brain glucose sensing has been demonstrated, but the study of upstream trafficking of glucose and its metabolites has never been undertaken. Moreover, the understanding of glucose fluxes through astroglial networks in metabolic diseases such as obesity or diabetes, where defects in brain glucose sensing are well characterized, might be of prime importance in the etiology of disturbed autonomic controls and/or food intake. Consequently, the objective of this project is to explore the causal links between metabolic trafficking through astroglial networks and hypothalamic glucose sensing mechanism at molecular, cellular and physiological levels.

The scientific project will try to reveal the key role, still largely neglected, displayed by the glial cells on neuronal activity control (in glutamatergic synapses). L'équipe émergeante, en cours de formation au sein du CSGA-UMR 1324, cherchera à développer des outils génétiques de pointe chez la drosophile, modèle biologique extrêmement puissant en neurogénétique. The emerging team, at the CSGA-UMR1324, will develop powerful genetic tools in Drosophila. The members of the team will investigate the impact of glia in the behavior (food uptake and courtship). They will highlight the cellular mechanisms implicated in chemoperception. The expected data are susceptible to touch a large scientific public since the important role of glutamate in the nervous system. Abnormal regulation of glutamate is known to be involved in several human diseases. Nevertheless, its physiological impact is still largely unknown when it is secreted by glial cells. We plan to reveal it.

The evolution of Earth's climate is currently matter of a critical scientific debate. Most models of future climates depend on understanding past climates. It is therefore essential to determine the factors influencing climate, and their respective roles. Silicate weathering is one of the two main sinks of atmospheric greenhouse CO2 over large timescales. However, we are still unable to provide accurate estimates of present-day and past silicate weathering rates at continental scales. With recent technological developments, precise measurements of new isotope tracers are being developed in selected laboratories worldwide. This has opened a new route for investigating low temperature processes, in particular chemical erosion. Among these tracers, the stable isotopes of lithium and magnesium are most promising due to their fractionation during bio- or physico-chemical processes. However, at present, the specific processes responsible for Li and Mg isotope fractionation during water/rock interactions are poorly known. The purpose of this project is to bring new quantitative constraints on silicate chemical erosion, using these new proxies. The innovative aspect of this project is to undertake laboratory weathering experiments (collaborating with mineralogists and clay syntheses experts) in order to calibrate these tools and quantify the role of specific parameters such as runoff, temperature and vegetation. Then these proxies will be tested on natural well constrained weathering profiles. The proposed multidisciplinary project is situated at the boundary of three hitherto separate fields (isotope geochemistry, experimental mineralogy, biogeochemistry), all currently undergoing rapid expansion and development. The team brings together 3 young scientists (<36 yrs old), who started collaborating ~3 years ago, mainly in the context of an INSU project, and will benefit of international collaborations, and of the addition of a 4th young scientist, recently recruited for developing a new field linked to potassium isotope biogeochemistry.

The goal of this project is to develop the experimental and theoretical knowledge necessary to build a modeling of chemo-mechanical couplings at the micrometer scale. Because of their extremely high surface/volume ratio, MEMS devices and thin film materials are particularly subjected to the consequences of such surface-based couplings. Using the results of recent feasibility studies, one will simultaneously focus on : ->cases where the involved couplings degrade the functions normally satisfied by a component (permeation barriers for gas tanks) ; ->cases where new and innovative functions originate from these surface couplings (chemo-mechanical sensors for allergies).