La prise de décision motrice implique que le sujet analyse les différentes stratégies possibles, en se basant sur l’observation de son environnement notamment, qui le conduisent à une décision motrice finale la plus appropriée. Pour explorer ce processus, nous avons réalisé un projet de recherche qui a pour but de déterminer comment varie l’activité des cellules de trois différentes aires motrices du cortex cérébral, en fonction de plusieurs indices visuels observés lors du mécanisme de prise de décision complexe. Dans ce contexte, les indices sensoriels utilisés peuvent soit présenter des indices ambigus ou contradictoires en faveur de différents choix d’actions. Ce procédé nécessite à ce que le cerveau détermine à quel degré un indice sensoriel est plus en faveur d’un choix que d’un autre, et quel est le meilleur choix d’action à réaliser en se basant sur les indices sensoriels reçus durant une période de temps donnée. Dans ce projet de thèse nous avons enregistré l’activité des cellules des aires corticales motrices primaires (M1), du pré-moteur dorsal (PMd), et aussi du préfrontal dorso-latéral (DLPF), chez un singe, dans plusieurs tâches décisionnelles dont certaines ont été notamment utilisées au préalable au sein de notre laboratoire par Coallier et al. (2014,2015). Dans cette thèse, nous présenterons les observations obtenues dans le PMd. Dans les essais de nos différentes tâches, nous avons utilisé des stimuli visuels correspondants à des damiers multicolores composés d’un nombre variable de carrés bleus et jaunes. Ces damiers fournissaient différents niveaux « d’évidences » en faveur des cibles bleues ou jaunes, à atteindre en réalisant un mouvement du bras. Dans ce projet, nos hypothèses sont les suivantes: 1) l’activité des cellules du PMd est plus impliquée dans la sélection de l’action que dans les processus perceptuels de la tâche, 2) les cellules du PMd pourraient jouer un rôle dans les procédés métacognitifs tels que la confiance en des choix d’actions. En conclusion, nos expériences ont permis de mettre en évidence des mécanismes neuronaux à travers lesquels le cortex prémoteur dorsal (PMd) contribue à la planification et à l’exécution des mouvements volontaires du bras. Plus précisément, nos données montrent que le PMd est plus impliqué dans les aspects moteurs, que perceptuels de la prise de décision sensorimotrice. De plus, le PMd exprime une activité qui pourrait refléter des processus neuronaux par lesquels les singes font un suivi et évaluent leur propre performance dans les tâches, afin de prédire la probabilité de bonne réponse et de réussite de leurs décisions, et pour attribuer un niveau de confiance en leurs décisions. / Motor decision-making implies that the subject analyses different possible strategies, based on the observation of his environment in particular, which leads him to select the most appropriate final motor decision. To explore this process, we conducted a research project to determine how neural activity in the dorsal premotor cortex (PMd) varies according to several visual cues observed during a complex decision-making process. In this context, the sensory instructional cues used may either present ambiguous or even contradictory evidence in favor of different motor choices. This process requires the brain to determine to what degree sensory input is more in favor of one choice than another, and what is the best choice of action to take based on the sensory cues received over a given period of time. To do so, we recorded the activity of single neurons in the dorsal pre-motor cortex (PMd of a monkey, in several decision-making tasks, some of which were previously used in our laboratory by Coallier et al.(2014, 2015). We tested neural activity in our different tasks, by using visual stimuli that resembled multicolored checkerboards, composed of a variable number of blue and yellow squares. These checkerboards provided different levels of "evidence" in favor of blue or yellow targets, to be reached by moving the arm. In this project, our hypothesis are as follows: 1) PMd cell activity is more involved in action selection than in the perceptual processes of the task, 2) PMd cells could play a role in metacognitive processes such as confidence in action choices. In conclusion, our experiments provided new insights into the neural mechanisms by which the dorsal premotor cortex (PMd) contributes to the planning and execution of voluntary arm movements. In particular, our data show that PMd is more implicated in the motor aspects of sensorimotor decisions and expresses little or no activity related to the perceptual aspects of the decision-making process. Furthermore, PMd neurons express activity that might reflect neuronal processes by which the monkeys monitor and evaluate their performance in the tasks, in order to predict the probability of correct responses and success of their decisions, and to attribute a level of metacognitive confidence in their motor decisions.

Many primate populations face the threat of extinction due to habitat loss, intensive agriculture, hunting for meat, the pet trade and/or use in traditional medicines. An alternative approach to in situ conservation includes gene banking and the use of assisted reproductive technologies (ART), such as oocyte in vitro maturation (IVM) and in vitro fertilization (IVF). Although many of these 'high-tech' solutions have not yet been proven viable for pragmatic wildlife conservation, basic research and development of these emerging tools can provide necessary information needed to optimize these techniques and institute ART as a routine practice in conservation efforts. A severely limiting factor in the successful application of ARTs is the availability of mature developmentally competent oocytes. Oocyte maturation involves many nuclear and cytoplasmic factors, which can be affected by maturation conditions and female age. In vitro maturation does not have the same success rate across species studied. In primates especially, IVM oocytes exhibit reduced developmental capacity upon fertilization when compared to in vivo matured (IVO) oocytes. This study aimed to investigate possible causes of reduced developmental capacity of primate IVM oocytes using the rhesus macaque (Macaca mulatta) as a model. Research efforts included investigation of ovarian senescence, oocyte karyotype and spindle morphology, and establishment of an optimal sperm cryopreservation protocol for use in IVF. Histological examination of the rhesus ovary demonstrated an age-related pattern of follicle depletion similar to that described in the human ovary. Oocyte karyotype analysis revealed a significant effect of IVM on the frequency of hyperhaploidy. In addition, immunostaining and confocal microscopy demonstrated a significant increase of anomalous chromosome congression on the oocyte metaphase II spindle equator in relation to IVM and donor female age. These results indicate that IVM can produce serious, if not lethal consequences for embryo development. This study presents baseline data on ovarian aging in the rhesus macaque and aspects of nuclear maturation during macaque IVM that may contribute to the design of primate oocyte recovery plans. Implementation of either of two sperm cryopreservation methods originally developed for rhesus and vervet monkeys will aid future investigation of the developmental capacity of IVM oocytes.

Le traçage rétrograde des voies corticales chez le singe a permis d’étudier deux sujets liés. En premier lieu, des injections dans 40 aires d'un atlas cortical de 91 aires ont permis de constituer une base de données cohérente sur la connectivité corticale à l’échelle de l’hémisphère. Les structures sous-corticales favorisant la communication corticale via la formation de boucles cortico-sous-cortico-corticales ont été examinées. Nous montrons que la force des projections du claustrum (considéré comme ayant une affiliation étroite avec le cortex) vers chaque aire explorée est exceptionnelle. De plus, un chevauchement des neurones marqués dans le claustrum a été observé suite à des paires d'injections dans des aires largement éloignées, y compris dépourvues de connexions cortico-corticales directes. A l’aide d’outils de la théorie des graphes, nous avons examiné la centralité des 40 aires et du claustrum dans le réseau cortical. En particulier, le claustrum est le meilleur exemple d’une aire pouvant prétendre au statut de « hub ». Ces résultats soulignent l'importance d'étudier les principes organisationnels du cortex via l'analyse de la topologie de son réseau. En second lieu, nous avons étudié le développement de la voie corticospinale par laquelle le cortex influence la planification, l'exécution et le contrôle de la motricité fine. Nous montrons que la topologie des projections corticospinales chez l’adulte émerge suite à un processus développemental de raffinement des projections ipsi- et controlatérale étendues. Ces résultats suggèrent que le développement de la connectivité corticale pourrait être régulé de manière dynamique et spécifique aux primates / The retrograde tracing experiments in macaque cortex in this thesis had two related objectives. Firstly, injections in 40 cortical areas (from a 91-area atlas) allowed the construction of a hemisphere-wide consistent database of cortical connectivity. We examined which subcortical structures promote cortical communication via the formation of cortico-subcortical-cortical loops. The claustrum, which we argue has a tight affiliation with the cortex, showed uniquely strong outputs to every cortical area. Widely separated injection pairs led to overlapping labelled neurons in the claustrum including those pairs lacking direct cortico-cortical connections. Using graph theoretic tools, we examined how central the 40 areas and claustrum are in the cortical network, specifically with respect to hub status. This showed that the claustrum is, beyond doubt, the prime hub of the cortex. These findings emphasise the importance of studying the organizational principles of the cortex via the analysis of its network topology. Secondly, we investigated the development of the corticospinal pathway, a route over which the cortex directly influences the planning, execution and control of fine voluntary movements. We show that the adult pattern of corticospinal projections emerges via a developmental process from a widespread ipsi- and contralateral distribution. These findings suggest that the developmental refinement of cortical connectivity might be dynamically regulated and primate specific

Le promoteur viral module la transcription et par conséquent la réplication virale. Le promoteur du VIH-1 est polymorphe pour une variété de sites de fixation de facteurs de transcription, toutefois l'impact de ce polymorphisme sur la réplication virale in vivo n'est pas élucidé. Nous avons construit des virus chimères isogèniques portant le promoteur minimal des sous-types B, C, et E du VIH-1 dans le génome du VISmac239. Dans quatre macaques rhésus co-infectés avec les trois chimères, une discordance entre les génotypes des virus associés aux rPBMCs et des virions du sérum est observée lors de la primo-infection. Un changement dans le génotype viral est également visible entre la primo-infection et la phase asymptomatique. Nos résultats montrent que le polymorphisme du promoteur des sous-types du VIH-1 constitue un déterminant majeur pour la réplication et la dissémination virale, et que la virémie en primo-infection est majoritairement due à la réplication virale dans l'intestin.

Dominance rank often determines the share of reproduction an individual male can secure in group-living animals (i.e. dominance rank-based reproductive skew). However, our knowledge of the interplay between individual and social factors in determining rank trajectories of males is still limited. The overall aim of this thesis was therefore to investigate mechanisms that underlie individual dominance rank trajectories in male crested macaques (Macaca nigra) and to highlight potential individual and social determinants of how males can achieve and maintain the highest rank possible. Data for this thesis were collected on 37 males during a field study on a natural population of crested macaques living in the Tangkoko-Batuangus Nature Reserve in Indonesia. In study 1, I validate Elo-rating as a particularly well suited method to quantify dominance hierarchies in animal species with dynamic dominance relationships. In studies 2 and 3, I suggest a personality structure for crested macaque males consisting of five distinct factors and further demonstrate that two personality factors determine whether males will rise or fall in rank. Finally, in study 4, I present results on how males utilize coalitions to increase their future rank. Together, these results shed light on how individual attributes and social environment both can impact male careers. Ultimately, in order to understand what determines rank-based reproductive skew, we need to consider the complexity and likely diversity of the mechanisms underlying rank trajectories of individual males which are likely to differ across different species.

The current knowledge of the visual pathways in primates includes the patterns of projection from the retina through the dorsal lateral geniculate nucleus (dLGN) to the striate cortex (V1) and the extra-striate projections towards the dorsal and ventral streams. Cells with short wavelength sensitive cone (S-cone) inputs in the dLGN have been studied extensively in New World marmosets but not in Old World macaques. This thesis presents results from studies in the macaque monkey which are more relevant to humans since humans are closer in evolution to Old World than New World monkeys. / The spatial, temporal, chromatic and orientation preferences of neurons in the dLGN of the macaque were investigated by electrophysiological methods. The physiological findings of cells with S-cone inputs were compared to cells with opponent inputs from the long and medium wavelength sensitive cones (L-cones & M-cones, respectively). The cells receiving S-cone inputs (blue-yellow or B-Y cells) preferred lower spatial frequencies than the cells with opponent L-cone and M-cone inputs (red-green or R-G cells). Orthodromic latencies from optic chiasm stimulation were measured where possible to distinguish differences in conduction velocity between the cell groups. Although the B-Y cells usually had longer latencies than R-G cells, there wasconsiderable overlap between the cell groups. / The recorded cells were localised through histological reconstruction of dLGN sections stained for Nissl substance. The distribution of B-Y cells within the dLGN was compared to the distribution of R-G cells. The majority of B-Y cells were located within the intercalated koniocellular layers as well as the koniocellular bridges (extensions of the koniocellular layers into the adjacent parvocellular layers). The B-Y cells were also largely segregated within the middle dLGN layers (K3, P3, K4 & P4). The R-G cells were mainly concentrated within the parvocellular layers (P3, P4, P5 & P6) and were evenly distributed throughout the middle and outer layers of the dLGN. / The study also included recordings from the extra-striate middle temporal area (MT) to determine whether a fast S-cone input exists from the dLGN to area MT which bypasses V1. The pattern of cone inputs to area MT neurons was investigated before and during inactivation of V1. The inactivation was done through reversible cooling with a Peltier thermocouple device or focal inactivation with y-amino butyric acid (GABA) iontophoresis. Precise inactivation of V1 to the topographically matching visual fields of the recording sites in area MT revealed a preservation of all three coneinputs in many cells. The subcortical sources of these preserved inputs are discussed with their relevance to blindsight, which is the limited retention of visual perception after V1 damage. Analysis of the latencies of area MT cells revealed a rough segregation into latencies faster or slower than 70 ms. Cells both with and without a significant change in response during V1 inactivation were present in each group. The findings reported in this thesis indicate that some of the preserved inputs in area MT during V1 inactivation may be carried by a direct input from the dLGN which bypasses V1.

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5 ABSTRACT Object permanence is a cognitive ability to perceive the continuous existence of objects, even if they cannot be directly observed, respectively perceived by other senses (Piaget 1954). In humans object permanence develops in 6 qualitatively different stages. By using a comparative approach, it was found that the last stage 6 of this ability also occurs in great apes, gibbons and some New World monkeys (capuchin, marmoset and tamarin). In this study, we conducted a study with a series of invisible displacements of an object, in which we investigated whether two rhesus macaques (Macaca mulatta) have fully developed the ability of object permanence and don't rely on simple alternative cognitive strategies, while solving the different tasks. With one test subject, we confirmed that he solved the tasks with stage 6 object permanence abilities. Although the second individual reached significant performance in some sessions, the overall results are ambiguous, because during the testing he had a tendency to use simple alternative strategies. Our study concludes that under certain circumstances macaques have the cognitive capacity for a fully developed ability of object permanence. Key words: Object permanence, rhesus macaque, invisible displacement, cognitive functions

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