The West African chimpanzee is critically endangered throughout its range. The conservation of the species depends on the preservation of its habitat and on the accurate estimation of its population density, which is essential to the development of an appropriate management plan. Thus we monitored 136 chimpanzee nests in Fongoli (southeastern Senegal) between June 2022 and January 2024 in order to determine the plant species preferentially used for their construction, the main nesting habitats and the nest decay rate. This study reveals that chimpanzees in Fongoli mainly use Pterocarpus eurinaceus to build their nests. The different types of habitat in the study area are used periodically for nesting, with a marked preference for woodland savannas. Average nest height is7.2 ± 0.56 m, slightly lower than at other chimpanzee study sites in Senegal. The average lifespan of chimpanzee nests is 48.6 ± 2.2 days, and the rate of degradation depends on the season of construction, the physical characteristics of the nest trees and the types of habitat in which the nests are built. This research highlights the plant species and habitats essential to chimpanzee survival in Senegal. It also highlights the need for researchers to use site-specific nest decay rates to estimate ape population size.
Neuroscience research involving animal models is at the heart of major scientific questions. It provides considerable fundamental knowledge about biological mechanisms at the molecular, cellular and integrated levels, and enables the development of innovative therapeutic approaches. Although they represent only a small fraction of the animals used, non-human primates are an important model because of their phylogenetic proximity to humans. Similarities in physiology, neuroanatomy, reproduction, development, cognition and social complexity shared by primates make non-human primates ideal animal models for understanding human biology and developing new therapies. This proximity to humans is also a central point in ethical considerations regarding the place of non-human primates in neuroscience research. This review discusses recent developments in ethical approaches to the status of non-human primates.
The gray mouse lemur (Microcebus murinus), a small lemuriform Malagasy primate, exhibits relatively slow aging relative to its size (maximum observed longevity of nearly 14 years) with altered psychomotor abilities appearing at the age of 5 years. In some cases (~10%), aging is spontaneously accompanied by pathological cerebral alterations. We then observe some age-related deficits that are more severe than during aging without cerebral pathology, such as severe cognitive decline, marked cerebral atrophy, sometimes associated with an imbalance in glucose homeostasis, comparable with what is observed in humans. These age-related alterations have diverse origins that are sometimes poorly understood, and often multifactorial. Among the environmental factors involved in the establishment of these alterations, nutrition occupies a prominent place. In this paper, we will first present the changes occurring in cognitive and psychomotor functions during healthy and pathological aging in mouse lemurs. A summary of the cerebral, metabolic, and cellular alterations that occur during aging and their relationships with cognitive decline will be presented. As nutrition is one of the major environmental factors in the onset of age-related alterations, we will review the main anti-aging nutritional strategies with potential effects on brain functions that have been studied in this species. We will also present why the characteristics of this species make it a model of choice for anti-aging nutritional studies. This review will demonstrate that aging studies in mouse lemurs offer promising avenues of investigation for the understanding, prevention, and treatment of pathological aging in humans.
The Ebo forest covers about 140,000 hectares of coastal forest in the Littoral Region of Cameroon. It is one of the most ecologically rich forests in the Gulf of Guinea biodiversity hotspot. This forest, which harbors many globally threatened and endemic plant species, is also home to various emblematic fauna species. Based on a literature review and informal discussions with local communities, this study aims to provide current knowledge on the Ebo primate population, discuss their major threats at landscape level, and present current conservation efforts and perspectives on human-wildlife coexistence. The Ebo forest is rich in primates, featuring four nocturnal species (Galagoides thomasi, Arctocebus calabarensis, Sciurocheirus alleni, and Perodicticus edwardsi) and ten diurnal species, including two African great apes (Gorilla gorilla spp. and Pan troglodytes ellioti), one Drill (Mandrillus leucophaeus leucophaeus), one mangabey (Cercocebus torquatus), one colobus (Piliocolobus preussi), and five guenons (Allochrocebus preussi, Cercopithecus nictitans, C. mona, C. erythrotis, and C. pogonias). The Black and White monkey (Colobus guereza) is nowadays considered locally extirpated, and five other species are becoming rare or very rare. Hunting, wood extraction, slash-and-burn agriculture, and unplanned community resettlement represent the main anthropogenic threats to the Ebo primate community. There is a need for an appropriate integrated conservation strategy on the ground based on biological research and community-led conservation initiatives to safeguard the survival of Ebo primate populations. Additionally, inclusive land-use planning in this key biodiversity hotspot is a way to strategize for the long-term coexistence of humans and the Ebo primate assemblage.
In vivo gene therapies based on viral vectors, particularly recombinant adeno-associated viruses (rAAV), have become a promising approach for the treatment of various genetic diseases. However, the immune response against these vectors is still a major obstacle, affecting their efficacy and safety. This review examines the importance of non-human primates (NHPs) as translational models for the study of immune responses against rAAVs. After an overview of the characteristics of AAV vectors and the challenges posed by the translatability of animal models, we analyze the innate and adaptive immune responses to these vectors, highlighting the role of neutralizing antibodies and cytotoxic cells. We also discuss the severe adverse events observed in clinical trials, such as liver toxicity, thrombotic microangiopathy and neurotoxicity, and their correlation with preclinical studies on NHPs. Finally, we discuss strategies to improve the safety and efficacy of rAAV-based therapies, including immune modulation and optimization of preclinical models. All of these elements highlight the need to improve the translatability of preclinical results for better predictability of side effects and optimization of therapeutic protocols.
Spatial navigation disorders are among the earliest symptoms of neurodegenerative diseases such as Alzheimer’s. These deficits, partly linked to hippocampal degeneration, remain poorly understood in humans. Studies in rodents have revealed the existence of place cells and grid cells, which are key to spatial representations, and this discovery was awarded the 2014 Nobel Prize for the advance it represents for the understanding of neural computations. This model has shaped both clinical and experimental approaches, despite the lack of robust evidence in primates. However, the ecological niches of rodents and primates differ greatly, particularly since primates have largely readopted a predominantly diurnal lifestyle. These divergent evolutionary paths suggest possible neurological adaptations from rodents to primates. Recent work in macaques and marmosets questions the existence of a direct transposition of the hippocampal code: in primates, hippocampal cells appear to be involved in active visual processing using eye movements to look at different parts of space, rather than in the representation of the spatial position of the individual. This divergence highlights the need to reconsider the function of the hippocampus in primates, including humans. Such a reinterpretation could pave the way for diagnostic and experimental advances adapted to the specific neuronal representations in primates, and more generally underscores the importance of comparative studies for this purpose.
To understand the diversity of cognitive processes in primates, it is essential to consider the socio-ecological constraints they face in their natural environments. Laboratory studies have enabled detailed characterization of a range of neurocognitive processes in a few species—most notably humans and rhesus macaques. However, how these neurocognitive processes are mobilized under natural conditions, and how they vary across species in relation to their sociality and ecology, remains largely unknown. For several years, we have developed an interdisciplinary approach to address this complex question. This approach aims to identify potential links between 1) neurocognitive processes studied under controlled laboratory conditions in cognitive neurosciences, and 2) the socio-ecological factors that characterize the diversity of challenges encountered by different primate species in the wild. To do this, we used the volume of three specific prefrontal cortex regions as proxies for the importance of the cognitive operations in which each region is involved: the ventromedial prefrontal cortex (associated with decision-making and evaluation), the dorsolateral prefrontal cortex (associated with working memory), and the frontal pole (associated with metacognition). Our findings show that the volume variation in each of these regions is associated with distinct sets of socio-ecological variables, over and above the expected effects from phylogeny. We demonstrate how these specific relationships enable us not only to better understand the evolution of classic neuro-cognitive processes, but above all to combine the concepts of cognitive neurosciences and behavioural ecology to better understand the behaviour and cognition of primates in their natural environment.
The quality of human life depends in particular on the richness of social interactions. These interactions are made possible through the recognition and understanding of social signals and their conventions. This understanding is supported by social cognitive skills, which are recognized as one of the core functional domains that can be affected in neuropsychiatric, neurodevelopmental and neurodegenerative disorders. Disturbances of social cognition include impaired social perception, ineffective theory of mind, reduced empathy, or abnormal social behavior. From social perception to social cognition, all the way to social behaviors: research in non-human primate has been uniquely contributing towards identifying the neurobiological bases of social processes. In this review we highlight the relevance of these findings to our understanding of the workings of the social brain, with the goal of laying the foundation for developing better models of these impairments in patients and supplying human clinical neuroscience with valuable new hypotheses to understand how social mechanisms and access to them are disturbed in disease.
In France, in 2023, non-human primates (NHPs) accounted for only 0.17 % of animals used for scientific purposes. Although this figure is low compared to the use of other species, access to NHPs is now considered a major global geostrategic issue. These models are essential for understanding biological mechanisms, developing new therapies, and validating preclinical studies before proceeding to human trials. However, access to NHPs for research is currently under significant strain due to a combination of factors. Since 2020, China—formerly the world’s leading exporter of cynomolgus and rhesus macaques—has halted exports, triggering an unprecedented global shortage that has had a major impact on research programs. At the same time, commercial airlines such as Air France have ceased regular NHP transport due to pressure from animal protection groups. This has forced institutions to rely on chartered flights, which are up to ten times more expensive and require importing larger cohorts to offset the transport costs. Additionally, as of November 2022, the European Directive 2010/63/EU has imposed stricter requirements, limiting the use of NHPs to second-generation (F2) animals or those from self-sustaining colonies, thereby exacerbating supply constraints in Europe and creating a gap with less restrictive international regulations. Finally, the increasing pressure from activist groups against animal use in science—particularly involving NHPs—adds an additional layer of complexity and public scrutiny. In response to this challenging landscape, two French academic institutions are working to support the scientific community by pursuing two complementary strategies: the establishment of a national breeding center and the reinforcement of secure import channels from source countries.
Over the past five years, the human population has faced two distinct epidemics with varying health impacts: those caused by SARS-CoV-2 and the Mpox virus (MPXV). In response to these challenges, medical infrastructures were mobilized to care for patients, while preclinical research was simultaneously undertaken to develop infection models in various animal species, particularly Non-Human Primates (NHPs). Due to their physiological, genetic, and immune similarities to humans, NHPs are often considered the most suitable models for human infectious diseases. During the COVID-19 pandemic, the respiratory infection model in macaques enabled the testing of repurposed drugs already available on the market, as well as the first vaccines developed as early as 2020, which were then rapidly administered to humans. As for the 2022 Mpox outbreak, although it affected only a limited portion of the population, it led to the reactivation of infection models in macaques. These models can be used for current and future orthopoxvirus outbreaks, as well as in the context of protection against bioterrorism.
Emerging infectious diseases that threaten human populations require tools and models to study these diseases, which can help protect us. In response to the emergence of SARS-CoV-2, we have developed a non-human primate infection model to assess viral dynamics, pathophysiology, and immune response. Analyzing data collected in our laboratory from over 150 non-human primates (olive baboon, rhesus macaque and cynomolgus macaque), we compared SARS-CoV-2 infection by the Wuhan strain and several variants, including Delta and Omicron. Analyses show that the viral load peaks between 2 and 4 days after exposure to the virus. However, the intensity of the peak and the duration of detectable viral load are variant-dependent. Infection induces a transient decrease in lymphocyte numbers and inflammation, with elevated levels of IL-1RA (interleukin-1-receptor antagonist), IL-15 (interleukin-15), CCL-1 (chemokine C-C motif ligand-1) and haptoglobin in the plasma. Comparisons of the variants revealed that the Delta variant produced the highest viral loads and the most pronounced inflammatory response, while the Omicron variants exhibited attenuated virulence. The study of immune responses demonstrated the production of specific and neutralizing antibodies, with variations depending on the infectious variant. Notably, Omicron variants induced a delayed and less intense humoral response. In contrast, the cellular response of T lymphocytes showed strong cross-reactivity, with the production of interferon γ (IFN-γ) and IL-2 (interleukin-2). The cynomolgus macaque model has proven to be a highly relevant preclinical system for studying SARS-CoV-2 and evaluating therapeutic and vaccine strategies. This model has been instrumental in the identification of effective treatments and vaccines against COVID-19, and it remains a crucial reference point for investigating the ongoing evolution of the virus and associated immune responses.
The detection of an object in the visual field triggers an orienting gaze movement toward its location. This movement consists of a rapid rotation of the eyes, the saccade, which is accompanied by a slow eye movement if the target moves, and a head rotation if the object moves outside the limits of the oculomotor range. Over the seven past decades, technological developments have made it possible to measure, in parallel and with high temporal resolution, not only the single activity of one or more brain cells, but also eye and head movements in response to the presentation of various targets in the visual field. Extending discoveries made by their predecessors in the feline species, neurophysiologists and neuroanatomists have accumulated in non-human primates a considerable body of knowledge, which has made it possible to identify the brain networks involved in the production of eye movements and then, to understand the motor disorders exhibited by human patients suffering from brain dysfunction. In this article, we shall describe the neural networks that enable us to quickly and accurately direct our gaze toward visual targets located at different eccentricities and depths. We shall explain how research on monkeys has contributed to our understanding of the pathophysiology of human oculomotor disorders, and most importantly, has established a solid foundation of reliable knowledge. This foundation serves as a useful safeguard against the proliferation of pseudoscientific theories based on misinterpretations of correlations between eye movement parameters and cultural notions.
This case study explores early changes in cerebral perfusion after ischemic stroke induced by middle cerebral artery occlusion in a non-human primate model, in order to identify imaging markers predictive of functional recovery. Three animals with distinct lesion patterns were studied: one with a cortical lesion, another with a predominant striatal lesion and a third with a combined cortico-striatal lesion. Imaging techniques, including Fluid-attenuated inversion recovery magnetic resonance imaging and positron emission tomography with H2O and a tracer of inflammation (PK11195), were used to assess lesion volume, and gain insight into cerebral blood flow and inflammation. Functional recovery of the animals was assessed using a neurological deficit scoring grid for 30 days after occlusion. The results showed that, despite varying lesion locations, an early increase in cerebral perfusion in adjacent and contralateral regions, homologous to the lesion, as well as in structures of the medial wall (supplementary motor area, cingulate cortex) and cerebellum, was observed from occlusion and during reperfusion. These changes were associated with marked functional recovery. These data suggest that early cerebral perfusion in uninjured regions may be a key indicator of post-stroke functional recovery. This animal model of stroke via middle cerebral artery occlusion offers a valuable model for studying the neural mechanisms underlying functional recovery, highlighting the importance of activity in uninjured brain regions in the compensatory process.
Cognition is broadly defined as the set of mental processes involved in acquiring, processing, storing, and using information. It encompasses the mechanisms that allow individuals to interact with their environment, represent it mentally, and adapt to new situations. Cognitive functions span a wide range of mental activities, many of which are often complex and not clearly defined. This makes cross-species comparisons particularly challenging. Assessing cognition in non-human primates and understanding its diversity and evolutionary continuity across the animal kingdom remain significant scientific challenges. The advent of autonomous devices for evaluating cognitive abilities in animals has triggered a paradigm shift in research methodologies. These devices provide answers to the scientific, ethical, and ecological concerns associated with studying the animal mind. By employing interactive platforms, large numbers of subjects are encouraged to independently complete a wide array of cognitive tasks over extended periods, sometimes lasting several years. Integrating these tools into experimental designs enables more efficient data collection while respecting the animals' intrinsic motivation and reducing the need for human intervention. This article reviews the cognitive tests and measurements made possible by current autonomous systems and explores their potential applications in cognitive ethology, comparative psychology, neuroscience, and medicine. The use of such devices by non-human primates promotes the establishment of more naturalistic studies and fosters the emergence of novel multidisciplinary approaches. Crucially, these tools may help bridge the gap between study of animal cognition and methodologies traditionally employed in human disciplines, such as neuropsychology.
Research with non-human primates is crucial to advances in fundamental and clinical research. Similarities in the organisation and functioning of the nervous system are one of the keys to justifying the use of monkeys in behavioural neuroscience research. It is also a central point of ethical considerations concerning their place in neuroscience research. These ethical considerations have been translated into laws governing research. Nowadays, any use of animals must be carried out in accordance with the 3Rs principle, i.e. replace the use of animals by other methods whenever possible, reduce the number of animals used, and refine experimental procedures when these have to be carried out with an animal. This review presents the implementation of the refinement principle in neuroscience research involving monkeys. More specifically, we discuss developments implemented jointly by researchers, veterinarians and technicians to improve the care and welfare of monkeys involved in scientific protocols.
The grey mouse lemur is a primate endemic from Madagascar, which environmental conditions can vary from season to season, both predictably and unpredictably. To survive such difficult conditions, this small primate (weighing less than 100g) has developed both behavioral and physiological adaptive responses, which confer this species the metabolic flexibility to optimize its survival. The mouse lemur thus expresses a very marked seasonal phenotype, maintained in captivity, characterized by very large variations in body mass and metabolism. This seems to be accompanied by the existence of protective mechanisms to prevent the onset of metabolic disorders associated with overweight. Furthermore, males and females do not respond in the same way to environmental variations, in line with differences in energy requirements, particularly for reproduction. Our results confirm the importance of considering this factor in the study of organism-environment interactions. In this article, we present an integrative view of the metabolic, endocrine and molecular changes involved in the physiological regulations observed in the mouse lemur. The results presented describe both natural and spontaneous changes over the course of the seasons, as well as changes in response to a change in caloric intake, in terms of both quantity and quality, taking into account the effect of gender. This article will confirm that studies conducted on exotic non-model species, a fortiori primates, reveals exceptional phenotypes, shedding light on unique adaptive mechanisms, the understanding of which may help identify targets for therapeutic approaches in humans for the treatment of metabolic diseases.
Episodic memory impairments are a key feature of age-related cognitive decline. This study introduced a touch-screen task to assess the "what-where-which" components of episodic-like memory in marmosets (Callithrix jacchus). The task used naturalistic contexts featuring conspecific faces at specific locations, simulating an episodic memory scenario comparable to that in humans. Memory performance was compared across ages, in marmosets from two to seven years old (young-middle-aged) to eight years and up (older). Ten marmosets participated and were trained to be familiarized with faces and spatial locations. During testing, they were exposed to specific face-location-context associations and later they were required to recall these associations after short (two-day) and long-term (one-month) delays. Memory was assessed based on initial responses, correct answers, and error rates. We found that memory performance was primarily based on identity (face) rather than on spatial cues (location). Young-middle-aged marmosets performed significantly better than older animals, particularly in long-delay tests, suggesting an age-related decline in episodic-like memory. These results highlight memory deficits in aged marmosets, particularly for remote episodes, while younger marmosets demonstrated better memory consolidation and retrieval. This underscores the impact of aging on the association of context elements in episodic-like memory processes.
