Histoire de la découverte du cerveau et del’évolution des méthodes d’exploration : De la Préhistoire à nos jours

International audienceL'histoire des neurosciences montre que la découverte du système nerveux en général et du cerveau en particulier a été chaotique, émaillée de périodes de progrès et de reflux au fil des temps et des cultures. Pour mieux en saisir la portée, chaque étape dans les découvertes est replacée dans le contexte théorique de pensée qui les a présidées et en fonction des méthodes et des techniques d'exploration alors en usage. À partir de quel moment de l'Histoire, le cerveau a-t-il suscité l'intérêt de l'Homme ? Quand est-il devenu un sujet d'étude scientifique ? Il est bien sûr impossible de répondre avec précision à de telles questions, dans la mesure où nous ne disposons que de fort peu de données fiables surtout pour les temps les plus reculés. Mais cela ne nous empêche pas de faire le point de nos connaissances en la matière en périodisant les différentes cultures et civilisations et, pour chacune des périodes historiques, en relatant brièvement le contexte philosophique et socioculturel dans lequel telle technique d'exploration et telle découverte majeure ont pu être faites, quand elles ne sont pas, selon le cas, purement et simplement entravées

Hyperactive and anxiolytic‐like behaviors result from loss of COUP‐TFI/Nr2f1 in the mouse cortex

International audienceThe nuclear receptor COUP TFI (also known as Nr2f1) plays major roles in specifying distinct neuronal subtypes during patterning of the neocortical motor and somatosensory cortex, as well as in regulating the longitudinal growth of the hippocampus during development. In humans, mutations in the NR2F1 gene lead to a global developmental delay and intellectual disabilities. While more than 30% of patients show behavioral features of autism spectrum disorder, 16% of haploinsufficient children show signs of hyperactivity and impulsivity. Loss of COUP-TFI in the cortical mouse primordium results in altered area organization and serotonin distribution, abnormal coordination of voluntary movements and learning and memory deficits. Here, we asked whether absence of COUP-TFI affects locomotor activity, anxiety, as well as depression. Mice mutant for COUP-TFI have normal motor coordination, but significant traits of hyperactivity, which does not seem to respond to N-Methyl-D-aspartate (NMDA) antagonists. However, no changes in anxiety, despite increased locomotor performances, were observed in the open field task. On the contrary, elevated plus maze and dark-light test explorations indicate a decreased anxiety-like behavior in COUP-TFI mutant mice. Finally, significantly reduced immobility in the forced swim test and no changes in anhedonia in the sucrose preference task suggest no particular depressive behaviors in mutant mice. Taken together, our study shows that loss of COUP-TFI leads to increased locomotor activity but less anxiety and contributes in further deciphering the pathophysiology of patients haploinsufficient for NR2F1

Hippocampal train stimulation modulates recallof fear extinction independently of prefrontalcortex synaptic plasticity and lesions

It has been shown that long-term potentiation (LTP) develops in the connection between the mediodorsal thalamus (MD) and the medial prefrontal cortex (mPFC) and between the hippocampus (HPC) and the mPFC following fear extinction, and correlates with extinction retention. However, recent lesion studies have shown that combined lesions of the MD and mPFC do not interfere with extinction learning and retention, while inactivation of the dorsal HPC disrupts fear extinction memory. Here we found in rats that immediate post-training HPC low-frequency stimulation (LFS) suppressed extinction-related LTP in the HPC–mPFC pathway and induced difficulties in extinction recall. HPC tetanus, applied several hours later, failed to re-establish mPFC LTP but facilitated recall of extinction. Delayed post-training HPC LFS also provoked mPFC depotentiation and difficulties with extinction recall. HPC tetanus abolished these two effects. We also found that damage to the mPFC induced fear return only in rats that received HPC LFS following extinction training. HPC tetanus also reversed this behavioral effect of HPC LFS in lesioned rats. These data suggest that the HPC interacts with the mPFC during fear extinction, but can modulate fear extinction independently of this interaction

Numerical prediction of grain structure formation during laser powder bed fusion of 316 L stainless steel

International audienceAdditive Manufacturing (AM) processes enable the reduction of manufacturing time, material waste, and allows for the creation of complex structures. However, anisotropic mechanical behaviour is frequently observed in additively manufactured parts, and it is directly linked to the component's grain structure characteristics, which itself is dependent on the process parameters. The formation of grain structure in 316 L stainless steel fusion lines is investigated in this paper, combining experimental results and numerical simulations. Experimentally, fusion lines are built on a 316 L substrate, using an instrumented LPBF process. The high-speed camera recordings combined with the characterization of the samples enables capturing of melt-pool sizes and grain characteristics. The numerical modelling is based on a three-dimensional “CAFE” model, coupling Cellular Automata and Finite Element models to predict grain formation. The thermal model is defined and calibrated using the experiments. The experimental and numerical grain characteristics are compared. Numerical results are discussed with regards to the growth models and the process parameters. The growth model defined here is compared to existing models and is well fitted to capture grain formation in single-track configurations. Finally, the average grain size and aspect ratio of the grains increase with an increase of the process' linear energy

Numerical Prediction of Microstructures by a Coupled Model (CA-FE) for Laser Beam Melting of Single-Track 316L Stainless Steel

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Prefrontal high-frequency stimulation prevents sub-conditioning procedure-provoked, but not acute stress-provoked, reemergence of extinguished fear

We have recently shown that post-extinction exposure of rats to a sub-conditioning procedure (SCP, i.e. retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) or to acute stress provokes reemergence of extinguished fear. Furthermore, this SCP effect can be abolished by high-frequency stimulation (HFS) of the medial prefrontal cortex (mPFC), when applied following the SCP. The aim of the present study was to test whether HFS of the mPK is effective in preventing both SCP-induced and acute stress-provoked fear reemergence. Rats implanted with stimulating electrodes in the mPFC were trained to acquire high levels of freezing to conditioned auditory cue. This fear response was then extinguished. Three weeks later, no spontaneous recovery was observed, but rats exposed to either the SCP or acute stress again exhibited high levels of freezing. HFS of the mPFC, applied before provoking fear reemergence, prevented the effects of SCP, but not acute stress. These data suggest that acute stress may have more impact on functions of the mPFC and/or associated structures than a situational reminder of fear conditioning. (C) 2013 Elsevier Inc. All rights reserved

Post-extinction fluoxetine treatment prevents stress-induced reemergence of extinguished fear

The post-extinction exposure of rats to a sub-conditioning procedure (SCP; i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) has been reported to provoke the reemergence of extinguished fear. This phenomenon can be prevented by chronic fluoxetine treatment. We sought to examine another potential inducer of fear reemergence, acute stress, in rats and determine whether fluoxetine prevents this phenomenon. Because in previous studies fluoxetine was administered before extinction, we first analyzed its effect on the SCP-associated reemergence of auditory-cued conditioned fear in rats injected after extinction to avoid any interaction between fluoxetine and extinction learning. Next, we used the same protocol but replaced the SCP with acute stress. We found that the SCP and acute stress, which were carried out 3 weeks after fear extinction, similarly provoked the reemergence of extinguished fear in rats injected with vehicle during the 3-week period. In contrast, the animals treated with fluoxetine during this period behaved similarly to those not exposed to an inducer of fear reemergence. Our data establish acute stress as an inducer of fear reemergence. The results provide further support for the hypothesis that fluoxetine interfered with mechanisms that reactivated extinguished fear, even when administered after fear extinction

Prefrontal high-frequency stimulation prevents sub-conditioning procedure-provoked, but not acute stress-provoked, reemergence of extinguished fear

We have recently shown that post-extinction exposure of rats to a sub-conditioning procedure (SCP, i.e. retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) or to acute stress provokes reemergence of extinguished fear. Furthermore, this SCP effect can be abolished by high-frequency stimulation (HFS) of the medial prefrontal cortex (mPFC), when applied following the SCP. The aim of the present study was to test whether HFS of the mPK is effective in preventing both SCP-induced and acute stress-provoked fear reemergence. Rats implanted with stimulating electrodes in the mPFC were trained to acquire high levels of freezing to conditioned auditory cue. This fear response was then extinguished. Three weeks later, no spontaneous recovery was observed, but rats exposed to either the SCP or acute stress again exhibited high levels of freezing. HFS of the mPFC, applied before provoking fear reemergence, prevented the effects of SCP, but not acute stress. These data suggest that acute stress may have more impact on functions of the mPFC and/or associated structures than a situational reminder of fear conditioning. (C) 2013 Elsevier Inc. All rights reserved

France, Germany, and the Quest for European Strategic Autonomy: Franco-German Defence Cooperation in A New Era

Notes du Cerfa/Notes de l'Ifri 141Policy paper collectifHow can France and Germany contribute to reaching the goal of European strategic autonomy? This key question has been guiding the work with the present report. In the light of a more demanding security environment, but also a rare momentum for further European integration, Berlin and Paris have to take their security and defence cooperation to the next level, bilaterally as well as in the EU. Progress in Franco-German security and defence cooperation is a key step towards strategic autonomy with its three dimensions: political, operational and industrial autonomy. Political autonomy has so far been neglected in Franco-German security and defence cooperation. Past cooperation was almost exclusively linked to the operational, sometimes industrial levels. The new impetus needs to be embedded in a farther reaching political dialogue. This can best be achieved by elaborating a Franco-German White Paper on Security and Defence. At the operational level, the primary objective for Paris and Berlin is to enable Europeans to autonomously carry out the Petersburg tasks, as defined in article 43(1) of the Treaty of Lisbon. Nevertheless, the type of capabilities needed must be derived from a political analysis of the strategic environment and the threats posed. The same accounts for industrial autonomy where France and Germany should work towards closer cooperation and shared rules embedded in a political dialogue. With seven concrete recommendations, the paper aims to contribute to establishing strategic autonomy, starting at the bilateral level to provide leadership for an ambitious European project