Centre de Recherches sur la Cognition Animale

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

With the increasing size and frequency of mass events, the study of crowd disasters and the simulation of pedestrian flows have become important research areas. However, even successful modeling approaches such as those inspired by Newtonian force models are still not fully consistent with empirical observations and are sometimes hard to calibrate. Here, a cognitive science approach is proposed, which is based on behavioral heuristics. We suggest that, guided by visual information, namely the distance of obstructions in candidate lines of sight, pedestrians apply two simple cognitive procedures to adapt their walking speeds and directions. Although simpler than previous approaches, this model predicts individual trajectories and collective patterns of motion in good quantitative agreement with a large variety of empirical and experimental data. This model predicts the emergence of self-organization phenomena, such as the spontaneous formation of unidirectional lanes or stop-and-go waves. Moreover, the combination of pedestrian heuristics with body collisions generates crowd turbulence at extreme densities--a phenomenon that has been observed during recent crowd disasters. By proposing an integrated treatment of simultaneous interactions between multiple individuals, our approach overcomes limitations of current physics-inspired pair interaction models. Understanding crowd dynamics through cognitive heuristics is therefore not only crucial for a better preparation of safe mass events. It also clears the way for a more realistic modeling of collective social behaviors, in particular of human crowds and biological swarms. Furthermore, our behavioral heuristics may serve to improve the navigation of autonomous robots.

Human crowd motion is mainly driven by self-organized processes based on local interactions among pedestrians. While most studies of crowd behaviour consider only interactions among isolated individuals, it turns out that up to 70% of people in a crowd are actually moving in groups, such as friends, couples, or families walking together. These groups constitute medium-scale aggregated structures and their impact on crowd dynamics is still largely unknown. In this work, we analyze the motion of approximately 1500 pedestrian groups under natural condition, and show that social interactions among group members generate typical group walking patterns that influence crowd dynamics. At low density, group members tend to walk side by side, forming a line perpendicular to the walking direction. As the density increases, however, the linear walking formation is bent forward, turning it into a V-like pattern. These spatial patterns can be well described by a model based on social communication between group members. We show that the V-like walking pattern facilitates social interactions within the group, but reduces the flow because of its "non-aerodynamic" shape. Therefore, when crowd density increases, the group organization results from a trade-off between walking faster and facilitating social exchange. These insights demonstrate that crowd dynamics is not only determined by physical constraints induced by other pedestrians and the environment, but also significantly by communicative, social interactions among individuals.

In light of the rising prevalence of Alzheimer's disease (AD), new strategies to prevent, halt, and reverse this condition are needed urgently. Perturbations of brain network activity are observed in AD patients and in conditions that increase the risk of developing AD, suggesting that aberrant network activity might contribute to AD-related cognitive decline. Human amyloid precursor protein (hAPP) transgenic mice simulate key aspects of AD, including pathologically elevated levels of amyloid-β peptides in brain, aberrant neural network activity, remodeling of hippocampal circuits, synaptic deficits, and behavioral abnormalities. Whether these alterations are linked in a causal chain remains unknown. To explore whether hAPP/amyloid-β-induced aberrant network activity contributes to synaptic and cognitive deficits, we treated hAPP mice with different antiepileptic drugs. Among the drugs tested, only levetiracetam (LEV) effectively reduced abnormal spike activity detected by electroencephalography. Chronic treatment with LEV also reversed hippocampal remodeling, behavioral abnormalities, synaptic dysfunction, and deficits in learning and memory in hAPP mice. Our findings support the hypothesis that aberrant network activity contributes causally to synaptic and cognitive deficits in hAPP mice. LEV might also help ameliorate related abnormalities in people who have or are at risk for AD.

Although thousands of new neurons are continuously produced in the dentate gyrus of rodents each day, the function of these newborn cells remains unclear. An increasing number of reports have provided correlational evidence that adult hippocampal neurogenesis is involved in learning and memory. Exposure of animals to an enriched environment leads to improvement of performance in several learning tasks and enhances neurogenesis specifically in the hippocampus. These data raise the question of whether new neurons participate in memory improvement induced by enrichment. To address this issue, we have examined whether the increase in the number of surviving adult-generated cells following environmental enrichment contributes to improved memory function. To this end, neurogenesis was substantially reduced throughout the environmental enrichment period using the antimitotic agent methylazoxymethanol acetate (MAM). Recognition memory performance of MAM-treated enriched rats was evaluated in a novel object recognition task and compared with that of naive and nontreated enriched rats. Injections of 5-bromo-2'-deoxyuridine were used to label dividing cells, together with double immunofluorescent labelling using glial or neuronal cell-specific markers. We found that enrichment led to improved long-term recognition memory and increased hippocampal neurogenesis, and that MAM treatment during environmental enrichment completely prevented both the increase in neurogenesis and enrichment-induced long-term memory improvement. These results establish that newborn cells in the dentate gyrus contribute to the expression of the promnesic effects of behavioural enrichment, and they provide further support for the idea that adult-generated neurons participate in modulating memory function.

In animal societies as well as in human crowds, many observed collective behaviours result from self-organized processes based on local interactions among individuals. However, models of crowd dynamics are still lacking a systematic individual-level experimental verification, and the local mechanisms underlying the formation of collective patterns are not yet known in detail. We have conducted a set of well-controlled experiments with pedestrians performing simple avoidance tasks in order to determine the laws ruling their behaviour during interactions. The analysis of the large trajectory dataset was used to compute a behavioural map that describes the average change of the direction and speed of a pedestrian for various interaction distances and angles. The experimental results reveal features of the decision process when pedestrians choose the side on which they evade, and show a side preference that is amplified by mutual interactions. The predictions of a binary interaction model based on the above findings were then compared with bidirectional flows of people recorded in a crowded street. Simulations generate two asymmetric lanes with opposite directions of motion, in quantitative agreement with our empirical observations. The knowledge of pedestrian behavioural laws is an important step ahead in the understanding of the underlying dynamics of crowd behaviour and allows for reliable predictions of collective pedestrian movements under natural conditions.

BACKGROUND: Peptidergic neurons containing the melanin-concentrating hormone (MCH) and the hypocretins (or orexins) are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep) during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV) administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation. RESULTS: Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats). Further, we show that ICV administration of MCH induces a dose-dependent increase in PS (up to 200%) and slow wave sleep (up to 70%) quantities. CONCLUSION: These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.

Swarm robotics deals with the design, construction, and deployment of large groups of robots that coordinate and cooperatively solve a problem or perform a task. It takes inspiration from natural self-organizing systems, such as social insects, fish schools, or bird flocks, characterized by emergent collective behavior based on simple local interaction rules [1], [2]. Typically, swarm robotics extracts engineering principles from the study of those natural systems in order to provide multirobot systems with comparable abilities. This way, it aims to build systems that are more robust, fault-tolerant, and flexible than single robots and that can better adapt their behavior to changes in the environment.

Collective motion phenomena in large groups of social organisms have long fascinated the observer, especially in cases, such as bird flocks or fish schools, where large-scale highly coordinated actions emerge in the absence of obvious leaders. However, the mechanisms involved in this self-organized behavior are still poorly understood, because the individual-level interactions underlying them remain elusive. Here, we demonstrate the power of a bottom-up methodology to build models for animal group motion from data gathered at the individual scale. Using video tracks of fish shoal in a tank, we show how a careful, incremental analysis at the local scale allows for the determination of the stimulus/response function governing an individual's moving decisions. We find in particular that both positional and orientational effects are present, act upon the fish turning speed, and depend on the swimming speed, yielding a novel schooling model whose parameters are all estimated from data. Our approach also leads to identify a density-dependent effect that results in a behavioral change for the largest groups considered. This suggests that, in confined environment, the behavioral state of fish and their reaction patterns change with group size. We debate the applicability, beyond the particular case studied here, of this novel framework for deciphering interactions in moving animal groups.

The question of whether or not neural activity patterns recorded in the olfactory centres of the brain correspond to olfactory perceptual measures remains unanswered. To address this question, we studied olfaction in honeybees Apis mellifera using the olfactory conditioning of the proboscis extension response. We conditioned bees to odours and tested generalisation responses to different odours. Sixteen odours were used, which varied both in their functional group (primary and secondary alcohols, aldehydes and ketones) and in their carbon-chain length (from six to nine carbons). The results obtained by presentation of a total of 16 x 16 odour pairs show that (i) all odorants presented could be learned, although acquisition was lower for short-chain ketones; (ii) generalisation varied depending both on the functional group and the carbon-chain length of odours trained; higher generalisation was found between long-chain than between short-chain molecules and between groups such as primary and secondary alcohols; (iii) for some odour pairs, cross-generalisation between odorants was asymmetric; (iv) a putative olfactory space could be defined for the honeybee with functional group and carbon-chain length as inner dimensions; (v) perceptual distances in such a space correlate well with physiological distances determined from optophysiological recordings of antennal lobe activity. We conclude that functional group and carbon-chain length are inner dimensions of the honeybee olfactory space and that neural activity in the antennal lobe reflects the perceptual quality of odours.

Laboratory bioassays were conducted to evaluate the effects on honeybee behavior of sublethal doses of insecticides chronically administered orally or by contact. Emergent honeybees received a daily dose of insecticide ranging from one-fifth to one-five-hundredth of the median lethal dose (LD50) during 11 d. After exposure to fipronil (0.1 and 0.01 ng/bee), acetamiprid (1 and 0.1 microg/bee), or thiamethoxam (1 and 0.1 ng/bee), behavioral functions of honeybees were tested on day 12. Fipronil, used at the dose of 0.1 ng/bee, induced mortality of all honeybees after one week of treatment. As a result of contact treatment at 0.01 ng/bee, honeybees spent significantly more time immobile in an open-field apparatus and ingested significantly more water. In the olfactory conditioning paradigm, fipronil-treated honeybees failed to discriminate between a known and an unknown odorant. Thiamethoxam by contact induced either a significant decrease of olfactory memory 24 h after learning at 0.1 ng/bee or a significant impairment of learning performance with no effect on memory at 1 ng/bee. Responsiveness to antennal sucrose stimulation was significantly decreased for high sucrose concentrations in honeybees treated orally with thiamethoxam (1 ng/bee). The only significant effect of acetamiprid (administered orally, 0.1 microg/bee) was an increase in responsiveness to water. The neonicotinoids acetamiprid and thiamethoxam tested at the highest dose (one-tenth and one-fifth of their oral LD50, respectively) and fipronil at one-five-hundredth of LD50 have limited effects on the motor, sensory, and cognitive functions of the honeybee. Our data on the intrinsic toxicity of the compounds after chronic exposure have to be taken into account for evaluation of risk to honeybees in field conditions.

Activity-dependent synaptic plasticity and neurogenesis are two forms of brain plasticity that can participate in functional remodeling of neural networks during the formation of memories. We examined whether long-term potentiation (LTP) of excitatory synaptic transmission, a well characterized form of synaptic plasticity believed to play a critical role in memory formation, can regulate the rate of neurogenesis in the adult rat dentate gyrus in vivo. We first show that induction of LTP at medial perforant path-granule cell synapses stimulates the proliferation of progenitor cells in the dentate gyrus with a consequential long-term persistence of a larger population of surviving newborn cells. Using protocols to examine the effect of LTP on survival, we next show that LTP induction promotes survival of 1- to 2-week-old dentate granule cells. In no case did LTP appear to affect neuronal differentiation. Finally, we show that LTP induces expression of the plasticity-related transcription factor Zif268 in a substantial fraction of 2-week-old but not 1-week-old neurons, suggesting the prosurvival effect of LTP can be observed in the absence of LTP-mediated Zif268 induction in newborn cells. Our results indicate that electrically induced LTP in the dentate gyrus in vivo provides a cellular/molecular environment that favors both proliferation and survival of adult-generated neurons.

Extracellular electrophysiological recordings in freely moving cats have shown that serotonergic neurons from the dorsal raphe nucleus (DRN) fire tonically during wakefulness, decrease their activity during slow wave sleep (SWS), and are nearly quiescent during paradoxical sleep (PS). The mechanisms at the origin of the modulation of activity of these neurons are still unknown. Here, we show in the unanesthetized rat that the iontophoretic application of the GABA(A) antagonist bicuculline on dorsal raphe serotonergic neurons induces a tonic discharge during SWS and PS and an increase of discharge rate during quiet waking. These data strongly suggest that an increase of a GABAergic inhibitory tone present during wakefulness is responsible for the decrease of activity of the dorsal raphe serotonergic cells during slow wave and paradoxical sleep. In addition, by combining retrograde tracing with cholera toxin B subunit and glutamic acid decarboxylase immunohistochemistry, we demonstrate that the GABAergic innervation of the dorsal raphe nucleus arises from multiple distant sources and not only from interneurons as classically accepted. Among these afferents, GABAergic neurons located in the lateral preoptic area and the pontine ventral periaqueductal gray including the DRN itself could be responsible for the reduction of activity of the serotonergic neurons of the dorsal raphe nucleus during slow wave and paradoxical sleep, respectively.

Fish schooling is a phenomenon of long-lasting interest in ethology and ecology, widely spread across taxa and ecological contexts, and has attracted much interest from statistical physics and theoretical biology as a case of self-organized behaviour. One topic of intense interest is the search of specific behavioural mechanisms at stake at the individual level and from which the school properties emerges. This is fundamental for understanding how selective pressure acting at the individual level promotes adaptive properties of schools and in trying to disambiguate functional properties from non-adaptive epiphenomena. Decades of studies on collective motion by means of individual-based modelling have allowed a qualitative understanding of the self-organization processes leading to collective properties at school level, and provided an insight into the behavioural mechanisms that result in coordinated motion. Here, we emphasize a set of paradigmatic modelling assumptions whose validity remains unclear, both from a behavioural point of view and in terms of quantitative agreement between model outcome and empirical data. We advocate for a specific and biologically oriented re-examination of these assumptions through experimental-based behavioural analysis and modelling.

Spatial self-organization is the main theoretical explanation for the global occurrence of regular or otherwise coherent spatial patterns in ecosystems. Using mussel beds as a model ecosystem, we provide an experimental demonstration of spatial self-organization. Under homogeneous laboratory conditions, mussels developed regular patterns, similar to those in the field. An individual-based model derived from our experiments showed that interactions between individuals explained the observed patterns. Furthermore, a field study showed that pattern formation affected ecosystem-level processes in terms of improved growth and resistance to wave action. Our results imply that spatial self-organization is an important determinant of the structure and functioning of ecosystems, and it needs to be considered in their conservation.

The demonstration that progenitor cells in regions of the adult mammalian brain such as the dentate gyrus of the hippocampus can undergo mitosis and generate new cells that differentiate into functionally integrated neurons throughout life has marked a new era in neuroscience. In recent years, a wide range of investigations has been directed at understanding the physiological mechanisms and functional relevance of this form of brain plasticity. Our current knowledge of adult hippocampal neurogenesis indicates that the production of new cells in the brain follows a multi-step process during which newborn cells are submitted to various regulatory factors that influence cell proliferation, maturation, fate determination and survival. As details of the dynamics of morphological maturation and functional integration of newborn neurons in corticohippocampal circuits have become clearer, an increasing number of studies have examined how environmental and/or behavioural factors can modulate neurogenesis and affect hippocampal-dependent learning and memory. In this article we present an overview of recent literature that relates neurogenesis to hippocampal function on the basis of correlative studies investigating the modulation of neurogenesis by learning and behavioural experience, and the consequences of the loss of hippocampal neurogenesis for memory function. We also highlight experimental evidence that immature neurons exhibit unique electrophysiological characteristics and therefore may constitute a specific cell population particularly inclined to undergo activity-dependent plasticity. Moreover, we review recent work that reveals an unsuspected mechanistic link between synaptic plasticity and the proliferation and survival of new hippocampal neurons. From the present background of research, we argue that the incorporation of functional adult-generated neurons into existing neural networks provides a higher capacity for plasticity, which may favour the encoding and storage of certain types of memories. Depending on their birth date and maturation stage, new neurons might be implicated in the encoding/storage process of the task at hand or may help future learning experience. Finally, we highlight critical issues to be addressed in order to decipher the exact contribution of newly generated neurons to cognitive functions.

Spatial memory enhances an organism's navigational ability. Memory typically resides within the brain, but what if an organism has no brain? We show that the brainless slime mold Physarum polycephalum constructs a form of spatial memory by avoiding areas it has previously explored. This mechanism allows the slime mold to solve the U-shaped trap problem--a classic test of autonomous navigational ability commonly used in robotics--requiring the slime mold to reach a chemoattractive goal behind a U-shaped barrier. Drawn into the trap, the organism must rely on other methods than gradient-following to escape and reach the goal. Our data show that spatial memory enhances the organism's ability to navigate in complex environments. We provide a unique demonstration of a spatial memory system in a nonneuronal organism, supporting the theory that an externalized spatial memory may be the functional precursor to the internal memory of higher organisms.

Swarm robotics will tackle real-world applications by leveraging automatic design, heterogeneity, and hierarchical self-organization.

A fundamental question in nutritional biology is how distributed systems maintain an optimal supply of multiple nutrients essential for life and reproduction. In the case of animals, the nutritional requirements of the cells within the body are coordinated by the brain in neural and chemical dialogue with sensory systems and peripheral organs. At the level of an insect society, the requirements for the entire colony are met by the foraging efforts of a minority of workers responding to cues emanating from the brood. Both examples involve components specialized to deal with nutrient supply and demand (brains and peripheral organs, foragers and brood). However, some of the most species-rich, largest, and ecologically significant heterotrophic organisms on earth, such as the vast mycelial networks of fungi, comprise distributed networks without specialized centers: How do these organisms coordinate the search for multiple nutrients? We address this question in the acellular slime mold Physarum polycephalum and show that this extraordinary organism can make complex nutritional decisions, despite lacking a coordination center and comprising only a single vast multinucleate cell. We show that a single slime mold is able to grow to contact patches of different nutrient quality in the precise proportions necessary to compose an optimal diet. That such organisms have the capacity to maintain the balance of carbon- and nitrogen-based nutrients by selective foraging has considerable implications not only for our understanding of nutrient balancing in distributed systems but for the functional ecology of soils, nutrient cycling, and carbon sequestration.

Studies on human and animals shed light on the unique hippocampus contributions to relational memory. However, the particular role of each hippocampal subregion in memory processing is still not clear. Hippocampal computational models and theories have emphasized a unique function in memory for each hippocampal subregion, with the CA3 area acting as an autoassociative memory network and the CA1 area as a critical output structure. In order to understand the respective roles of the CA3- and CA1-hippocampal areas in the formation of contextual memory, we studied the effects of the reversible inactivation by lidocaine of the CA3 or CA1 areas of the dorsal hippocampus on acquisition, consolidation, and retrieval of a contextual fear conditioning. Whereas infusions of lidocaine never impaired elementary tone conditioning, their effects on contextual conditioning provided interesting clues about the role of these two hippocampal regions. They demonstrated first that the CA3 area is necessary for the rapid elaboration of a unified representation of the context. Secondly, they suggested that the CA1 area is rather involved in the consolidation process of contextual memory. Third, they showed that CA1 or CA3 inactivation during retention test has no effect on contextual fear retrieval when a recognition memory procedure is used. In conclusion, our findings point as evidence that CA1 and CA3 subregions of the dorsal hippocampus play important and different roles in the acquisition and consolidation of contextual fear memory, whereas they are not required for context recognition.