Vers une meilleure gestion du lapin en tant qu’animal de laboratoire : état des lieux et perspectives

The rabbit is an essential model in scientific research, particularly in the study of cardiovascular diseases such as hypertension and atherosclerosis and for the investigation of the osteoarticular system. Due to the fact that various factors (environmental, microbial, stress, pain.) can influence data obtained from experiments, special care must be given to housing conditions. Sensory enrichment (olfactive, auditive, visual or tactile stimuli) and physical enrichment (nutritional and social stimuli) allow rabbits to express specific behaviours and reduce stereotypies. This synthesis reminds of the importance of these factors and gives to the researcher some ways to control them.Le lapin est un modèle essentiel en recherche scientifique, en particulier dans l’étude des maladies cardiovasculaires, telles l’hypertension et l’athérosclérose, et les investigations menées sur le système ostéo-articulaire. Divers facteurs (environnement, statut microbien, stress, douleur) peuvent induire de sérieuses répercussions sur la collecte des données expérimentales. La prise en compte de ces facteurs et leur maîtrise est indispensable à l’obtention de données reproductibles. Une attention particulière doit être accordée aux conditions d’hébergement. L’enrichissement sensoriel (stimuli olfactifs, auditifs, visuels, tactiles) et l’enrichissement physique (stimuli nutritionnels et sociaux : hébergement en groupe) permettent aux animaux d’exprimer de nombreux comportements spécifiques et de réduire les stéréotypies. Cette synthèse rappelle l’importance de ces facteurs et donne quelques recommandations aux chercheurs pour mieux les contrôle

Les protéines de choc thermique (heat shock proteins). I : Classification, structure, fonctions et implications dans les processus pathologiques

All living systems have evolved mechanisms to maintain homeostasis in the face of rapid environmental changes. When exposed to elevated temperatures, most of the cells activate the synthesis of a specific group of proteins called Heat Shock Proteins (Hsps). This heat shock response, under control of specific transcription factors, the Heat Shock factors (HSF), is an evolutionarily conserved mechanism, from bacteria to humans. Heat Shock Proteins are classified into families according to their molecular weight (Hsp 25, 40, 70, 90, 105). They play the role of molecular chaperones by binding and protecting other molecules (proteins, RNAs). The function of Hsp is to prevent accumulation of non-native proteins either by assisting proper folding of polypeptides or by driving them to proteosome pathway for degradation. Hsps are involved in various pathological processes that are accompanied by protein alterations such as chronic or degenerative diseases. This review describes structural and functional characteristics of the six main Hsps classes. It also focuses on their respective role in highly studied pathologies. The diversity of Hsps implications in these diseases explains that they became recently a strategic target in development of new therapeutic strategies.Tout organisme est doté de mécanismes lui permettant de résister à de brusques changements de son environnement. Exposées à une température anormalement élevée, la plupart des cellules activent l’expression d’une classe particulière de protéines appelées les protéines de choc thermique (Heat Shock Proteins, Hsps). Cette réponse cellulaire au choc thermique placée sous le contrôle de facteurs de trans-cription spécifiques, les facteurs de choc thermique (Heat shock factor, HSF) est un mécanisme conservé au travers de l’évolution depuis les bactéries jusqu’à l’homme. Les protéines de choc thermique qui sont divisées en familles désignées par leur masse moléculaire (Hsp25, 40, 70, 90, 105) font partie des molé-cules chaperons qui s’associent à d’autres molécules (protéines, ARNs) et en protègent la destinée. Le rôle des Hsp est d’empêcher l’accumulation de protéines anormales en aidant à conformer correctement les polypeptides ou en les dirigeant vers le protéosome qui les détruit. En tant que chaperons, les Hsp sont impliquées dans de nombreux processus pathologiques qui s’accompagnent d’altérations des protéines comme les maladies chroniques et dégénératives. Cette revue décrit les spécificités structurelles et fonc-tionnelles des six familles principales d'Hsp ainsi que leur intervention à différents niveaux dans les patho-logies les mieux étudiées. La multiplicité de l'implication des Hsp dans ces phénomènes pathologiques les désigne comme cibles privilégiées dans le développement de nouvelles stratégies thérapeutiques

Resident CD11b(+)Ly6C(-) Lung Dendritic Cells Are Responsible for Allergic Airway Sensitization to House Dust Mite in Mice.

peer reviewedConventional dendritic cells (DCs) are considered to be the prime initiators of airway allergy. Yet, it remains unclear whether specific DC subsets are preferentially involved in allergic airway sensitization. Here, we systematically assessed the respective pro-allergic potential of individually sorted lung DC subsets isolated from house dust mite antigen (HDM)-treated donor mice, following transfer to naive recipients. Transfer of lung CD11c(+)CD11b(+) DCs, but not CD11c(+)CD11b(-)CD103(+) DCs, was sufficient to prime airway allergy. The CD11c(+)CD11b(+) DC subpopulation was composed of CD11c(+)CD11b(+)Ly6C(+) inflammatory monocyte-derived cells, whose numbers increase in the lungs following HDM exposure, and of CD11c(+)CD11b(+)Ly6C(-) DCs, which remain stable. Counterintuitively, only CD11c(+)CD11b(+)Ly6C(-) DCs, and not CD11c(+)CD11b(+)Ly6C(+) DCs, were able to convey antigen to the lymph nodes and induce adaptive T cell responses and subsequent airway allergy. Our results thus support that lung resident non-inflammatory CD11c(+)CD11b(+)Ly6C(-) DCs are the essential inducers of allergic airway sensitization to the common aeroallergen HDM in mice

Memory consolidation facilitated by burst-driven late-phase plasticity

peer reviewedHow do alternating periods of learning and rest contribute to memory consolidation? While it is recognized that learning relies on synaptic plasticity triggered by the spiking activity correlation between neurons, the role of rest periods and their biophysical mechanisms remain elusive. In this work, we leverage the interaction between the brain state fluctuations, reflecting changes in neuronal excitability, and memory, relying on synaptic plasticity occurring at different phases. Our approach involves a neural network model capable of transitioning between learning periods characterized by fast low-amplitude oscillations, and rest periods marked by slower large- amplitude oscillations. At the neuronal level, it is characterized by biophysical neurons capable of switching between input-driven tonic firing and the less-explored collective bursting. In our model, synapses exhibit calcium-based early-phase plasticity, as studied in previous work. Here, we propose a new additional burst-induced late-phase plasticity mechanism. During learning, the early-phase plasticity forms new memories, as traditionally observed. During rest, the early-phase plasticity resets, returning to its baseline set point. It provides a physiological trace to drive the late-phase plasticity facilitating memory consolidation. Validating our model through a memory task utilizing the MNIST dataset, we demonstrate that switching from tonic to burst, combined with early- and late-phase plasticity enables the network to acquire new information while preserving existing memories. The collective bursting activity during rest, combined with late-phase plasticity, represents the generation of new postsynaptic proteins and morphological synapse changes (termed structural plasticity). We find that substituting rest with an additional learning period impedes memory consolidation, rendering it susceptible to noise. These findings propose a potential biological mechanism for unsupervised memory consolidation during rest and explain how the brain balances synaptic homeostasis and memory processes. Moreover, they suggest the utility of incorporating rest periods into machine learning models, highlighting the importance of including collective bursting and structural plasticity.3. Good health and well-bein

The endogenous nature of bursting leads to homeostatic reset in synaptic weights: a key player to regularize network connectivity during sleep

editorial reviewedLearning and memory rely on the ability of neurons to form new connections, a property called synaptic plasticity. Synaptic connections can be strengthened or weakened via plasticity rules sensitive to neuronal firing. Simultaneously, brain information processing is shaped by fluctuations in neuronal activities, defining brain states. A well-known example of brain state switches is the transition from wakefulness to sleep. It is characterized by a change in population rhythm from active to oscillatory state, while at the cellular level neurons switch from tonic to burst. Altogether, it raises the question of how changes in neuronal activity affect memory formation and more precisely how switches from tonic to burst impact synaptic plasticity. To investigate this question, we used a cortical network built with conductance-based neuron models able to switch between tonic and burst. The synaptic connections within the network are plastic. They are driven either by phenomenological rules, such as pair-based [Pfister,2006] or calcium-based rules [Graupner,2016]. These rules are fitted on experimental data [Sjostrom,2001]. We showed that a switch to burst reminiscent of sleep leads to a homeostatic reset of synaptic weights, meaning that all weights converge towards a basal value. Here, we developed analytical analyses to understand the mechanisms underlying this reset and predict its value. For phenomenological plasticity rules, potentiation and depression balance leading to a converging point for the synaptic weight. The burst induces a homogeneous spike train correlation between pre and postsynaptic firing activity thanks to the stationarity during sleep. By contrast, in wakefulness, the correlation is highly heterogeneous. It comes from the variability in spiking activity used for the quick processing of incoming information such that no equilibrium is reached. A similar analysis is derived for calcium-based rules. The burst of action potential drives homeostatic fluctuations in calcium activity. Once again, the burst generates a balance between potentiation and depression unreached during wakefulness. Altogether, the mechanisms of the synaptic reset are rooted in the endogenous nature of the sleep-like bursting activity. Additionally, we show that the homeostatic reset is robust to neuronal variability and network heterogeneity. The sleep-dependent reset could play a central role in sleep homeostasis and sleep-dependent memory consolidation

The use of an adapted model allows contributing to the “Reduction” of mice used in experimental protocols: the case of the apoE–deficient (apo E-/-) mice in a model of atherosclerosis control

Atherosclerosis is a chronic vascular disease whose development is influenced by several mediators 1. Among them, the prostanoids large family lipids generated from the metabolism of arachidonic acid by the action of COX includes various types of PGs and thromboxane. Thromboxane A2 and PGI2 are present in abnormally elevated concentration in atherosclerosis 2-3. To exert its effects TXA2 and its precursor PGH2 act at a specific receptor termed TP receptor 4. As a result, TXA2 synthase inhibitors and TP antagonists have been developed to reduce and to prevent TXA2 production and actions, respectively. The present study was undertaken in order to investigate whether BM-573, an original sulfonylurea derivate synthesized in our lab 5, and aspirin would be effective in preventing the progression of atherosclerosis in an apo E deficient mouse model.Evaluation de l’effet de modulateurs originaux du thromboxane A2 (TXA2) dans un modèle murin d’athéroscléros

Evaluation de l’utilisation du pepsinogène sanguin comme biomarqueur de l’intégrité de la muqueuse gastrique chez le porc. 2. Méthodes de dosage et intérêt en pathologie porcine

Pepsinogen is one component of the gastric juice which participes in the digestion. This macromolecule enters the blood circulation in a small measurable quantities in healthy subjects. Therefore, blood pepsinogen is claimed to be an indicator of the integrity of the gastric mucosa. This paper was written to review the use of porcine in the diagnostic of stomach ulcers and Hyostrongylus rubidus infection. The methods of measurement of blood pepsinogen and the diagnostic values are discussed.Le pepsinogène est une composante du suc gastrique qui participe à la digestion des protéines alimentaires. Il est aussi parmi les macromolécules qui entrent dans la circulation sanguine en faibles quantités mesurables chez des sujets normaux. Son dosage est utilisé dans la mise en évidence de certaines pathologies gastriques chez le porc. Cette synthèse décrit les méthodes de dosage et des valeurs sériques ou plasmatiques du pepsinogène en relation avec des ulcères ou les infestations parasitaires à Hyostrongylus rubidus chez le por

Unraveling the role of collective bursting neurons, quiet waking, and structural plasticity in memory consolidation using a computational approach

editorial reviewedWhen memorizing new information, it is commonly accepted that breaks associated with brain rest can improve performance. We investigate this hypothesis using a computational approach. Our neural network, composed of conductance-based model neurons, simulates brain states, transitioning from active learning to quiet waking. It corresponds to a neuronal switch from tonic firing to collective bursting orchestrated by neuromodulators. Simultaneously, the network modifies synaptic weights through plasticity to encode new memories. Recent findings reveal a homeostatic reset induced by collective bursting across various traditional synaptic plasticity rules (pair-based, triplet, or calcium-based rule). Unintuitively, strong weights depress, and weak weights potentiate during bursting until a set point is reached, causing forgetting but also restoring synaptic weights and facilitating new memory formation. We propose a structural plasticity rule that complements traditional synaptic plasticity rules governing early-stage Long-Term Potentiation (E-LTP) and provides insights into late-stage Long-Term Potentiation (L-LTP). In our study, we demonstrate the efficacy of this novel mechanism across diverse memory tasks. Initially, we observe that quiet waking underlying collective bursting enhances the Signal-to-Noise Ratio in a pairing memory task. Moving on to a pattern recognition task, the network adeptly learns to identify small patterns, whether overlapping or not. We thoroughly analyze the evolution of receptive fields, represented by pattern-associated weight matrices, during switches from active learning to quiet waking states. Remarkably, during quiet waking periods, memory consolidation occurs without any pattern recall. Extending this approach to the MNIST recognition task leads to notable improvements in performance. In all tasks, blocking quiet waking states decreases the ability to consolidate memory. In conclusion, combining quiet waking with bursting neurons and structural plasticity improves learning and memory consolidation. This research aims to inspire investigations into the biophysical mechanisms of quiet waking in memory and the potential integration of resting states in machine learning algorithms for artificial intelligence.3. Good health and well-bein