Cognition allows animals to acquire, process, and store sensory information from the environment and use it to adapt to their surroundings. A battery of behavioral tests was used to assess the cognitive abilities of black-handed spider monkeys (Ateles geoffroyi). Black and white cups were used to assess (1) object permanence by showing the animals under which cup the reward was placed, (2) associative learning by concealing where the reward was placed, and (3) long-term memory by repeating the second task after a 4-month break; petri dishes with varying amounts of food were used to assess (4) relative quantity discrimination; and boxes fitted with dotted cards were used to assess discrete number discrimination with (5) equallysized dots and (6) various-sized dots. For each task, one session comprised 10 trials (i.e. responses). All nine animals succeeded in all tests and, as a group, reached the learning criterion of 70% correct responses on session two in the object permanence and associative learning tasks; on session eleven in the quantity discrimination task; on session sixteen in the numerosity task with equally-sized dots; on session three in the numerosity task with various-sized dots; and averaged 84.4% correct responses in the long-term memory task. Their prompt high score in the numerosity task with various-sized dots suggests that the animals acknowledged the task for its numerical properties as opposed to the size or pattern of the dots. These cognitive abilities are thought to shape the necessary behaviors for the ecological and social needs of the species.

After vasectomy, the passage of sperm antigen through the epithelium of the efferent duct in the rhesus macaque probably results in immune complex deposition. Immune complexes can be visualized in the thickened basement by fluorescence microscopy. Subsequent electron microscopic evaluation, with the appearance of electron-dense deposits in the basement membrane of the efferent ducts, substantiates these findings.

No description available.

La présence du système endocannabinoïde (eCB), en particulier le récepteur CB1 (CB1R), dans la rétine, le corps genouillé latéral, et l’aire visuelle primaire (V1) du singe a récemment été mise en évidence. Cependant, aucune étude n’a démontré la présence de ce système dans l’aire visuelle secondaire V2, une région qui reçoit la plupart des efférences de V1. Comme V1 exprime ce récepteur, nous faisons l’hypothèse que l’aire V2 l’exprime également. Le but de notre étude est donc de caractériser l’expression et la localisation cellulaire de ce système dans l’aire V2 du singe vervet. Des cerveaux de cinq singes vervets (Chlorocebus sabeus) adultes ont été utilisés. Les marqueurs cellulaires NeuN, SMI-32, et PV ont été employés pour caractériser et identifier les différentes couches de V2. En localisant ces derniers, nous déterminons la distribution de CB1R et des enzymes de synthèse (NAPE-PLD) et de dégradation (FAAH) du système eCB en utilisant des techniques d’immunofluorescence. De plus, l’organisation laminaire en six couches de V2 a été mise en évidence par nos marqueurs cellulaires. Nos résultats démontrent la présence de CB1R dans les fibres axonales aux extrémités de V2, c’est-à-dire dans les couches superficielles (1-3) et profondes (5-6). CB1R est peu ou pas exprimé dans la couche 4. CB1R entoure, mais n’est pas exprimé par les cellules positives- NeuN, SMI-32 et PV. Cependant, les enzymes NAPE-PLD et FAAH sont présentes dans les cellules pyramidales SMI-32 et les cellules interneurones PV -positives. Ces données indiquent que CB1R, NAPE-PLD et FAAH sont présentes dans V2 et pourraient moduler l’information visuelle provenant de V1 et se dirigeant vers les aires V4 et V5, et probablement, influencer la perception visuelle. / The presence of the endocannabinoid system in the retina, the lateral geniculate body, and the primary visual area (V1) of the monkey has recently been established. However, no study has demonstrated the presence of this system in area V2, a region that receives most of the afferents from V1. As V1 expresses this system, we assume that the area V2 also expresses it. The aim of our study is to characterize the expression and cellular localization of this system in the visual cortex V2 of the vervet monkey. The brains of 5 adult monkeys were used in this project. Cellular markers NeuN, SMI-32, and PV were used to characterize and identify the layers of V2. Using immunofluorescence, these markers were also localized in order to study the distribution of CB1R, the enzyme of synthesis (NAPE-PLD) and of degradation (FAAH) of eCB ligands. The six-layer organization of V2 was also identified by our cellular markers. Our results show the presence of the eCB system in area V2. Furthermore, we found that CB1R immunoreactivity is present in the axonal fibers at the ends of V2; in the superficial (L1-3) and deep (L5-6) layers. CB1R expression was low to non-existence in layer 4. CB1R surrounds but does not co-localize with NeuN-, SMI-32-, and PV- positive cells. On the other hand, NAPE-PLD and FAAH enzymes were co-localized with SMI-32-positive pyramidal cells and PV-positive interneuron cells. These data, therefore, indicate that CB1R, NAPE-PLD and FAAH are present in V2 and their presence can modulate visual information coming from V1 and going to V4 and V5, and probably, influence visual perception.

Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management.

Background: Chronic gastroenteropathies, including gluten sensitivity and marmoset wasting syndrome, frequently occur in captive colonies of common marmosets (Callithrix jacchus). Early identification and diagnosis of affected animals are desirable. Endoscopic examination of the colon in marmosets is described, but the small intestine can harbor significant mucosal lesions not representing those in the colon. Evaluating the small intestine currently requires invasive surgical biopsies due to the small patient size, carrying a risk of severe complications. Methods: Endoscopic intubation and multisite biopsy of the duodenum/proximal jejunum are demonstrated in 10 marmosets under general anesthesia. Results: Esophagogastroduodenoscopy with colonoscopy efficiently aid in examining the gastrointestinal tract and obtaining an antemortem histologic diagnosis in marmosets with chronic gastrointestinal signs. Conclusions: This minimally invasive technique is feasible in marmosets. Future investigations into the pathogenesis of chronic gastroenteropathies will benefit from these data, leading to improved animal welfare and better individual and colony health management

The lateral prefrontal cortex (LPFC) and the anterior cingulate cortex (ACC) are two key regions of the frontal executive control network. Ascending cholinergic pathways differentially innervate these two functionally distinct cortices to modulate arousal and motivational signaling for higher-order functions. The action of acetylcholine (ACh) in sensory cortices is constrained by layer, anatomical cell type, and subcellular localization of distinct receptors, but little is known about the nature and organization of frontal-cholinergic circuitry in primates. In this dissertation, we characterized the anatomical localization of muscarinic acetylcholine receptors (mAChRs), m1 and m2–the predominant subtypes in the cortex–and their expression profiles on distinct cell types and pathways in ACC and LPFC of the rhesus monkey, using immunohistochemistry, anatomical tract-tracing, whole cell patch-clamp recordings, and single nucleus RNA sequencing. In the first series of studies (Chapter 2), we used immunohistochemistry and high-resolution confocal microscopy to reveal regional differences in m1 and m2 receptor localization on excitatory pyramidal and inhibitory neuron subpopulations and subcellular compartments in ACC (A24) versus LPFC (A46) of adult rhesus monkeys (Macaca mulatta; aged 7-11 yrs; 4 males and 2 females). The ACC exhibited a greater proportion of m2+ inhibitory neurons and a greater density of presynaptic m2+ receptors localized on inhibitory (VGAT+) terminations on pyramidal neurons compared to the LPFC. This result suggests a greater cholinergic suppression of GABAergic neurotransmission in ACC. In a second set of experiments (Chapter 3), we examined the heterogeneity of m1 and m2 laminar expression in functionally distinct ACC areas A24, A25, and A32. These differ in their connections with higher order cortical areas and limbic structures, such as the amygdala (AMY). The density of m1+ and/or m2 expressing (m1+/m2+) pyramidal neurons was significantly greater in A24 compared to A25 and to A32, while A25 exhibited a significantly greater density of m2+VGAT+ terminals. In addition, we examined the substrates for cholinergic modulation of long-range cortico-limbic processing using bidirectional neural tracers to label one specific subtype, the AMY-targeting projection neurons in these ACC areas. Compared to A24 and A32, the limbic ventral A25 had a greater density of m1+/m2+ AMY-targeting pyramidal neurons across upper layers 2-3 and deep layers 5-6, suggesting stronger cholinergic modulation of amygdalar outputs. Lastly (Chapter 4), we assessed the functional effects of cholinergic modulation on excitatory and inhibitory synaptic activity as well as the molecular signatures related to m1 and m2 receptor expression. In experiments using in vitro whole-cell patch-clamp recordings of layer 3 pyramidal neurons in ACC and LPFC, we found that application of the cholinergic agonist carbachol (CCh) significantly decreased the frequency of excitatory postsynaptic currents (EPSCs) to a greater extent in ACC A24 than in LPFC A46. Using single nucleus RNA sequencing, we found that enriched m1 and m2 transcriptional profiles in distinct cell-types and frontal areas (ACC A24 and LPFC A46) had differentially expressed genes associated with down-stream signaling cascades related to synaptic signaling and plasticity. Together, these data reveal the anatomical, functional, and transcriptomic neural substrates of diverse cholinergic modulation of local excitatory and inhibitory circuits and long-range cortico-limbic pathways in functionally-distinct ACC and LPFC frontal areas that are important for cognitive-emotional integration.

A gene x environment interaction exists in the expression of anxiety for both human and nonhuman primates, such that individuals who are carriers of the (s) allele of the serotonin transporter genotype ( 5-HTT LPR) and exposed to early life stress are more at risk for exhibiting anxiety. The hypothalamic-pituitary-adrenal (HPA) axis has also been implicated in anxiety disorders but the relationship between early life/genotype, HPA activity, and anxiety is not well understood. Further, studies linking the HPA axis to anxiety have relied on "point" samples (blood and salivary cortisol) which reflect moments in time rather than long-term activity. The purpose of this dissertation was three fold: (1) to examine anxious behavior in monkeys with different 5-HTT LPR genotypes and rearing environments across the first two years of life, (2) to compare long-term HPA activity (as measured with hair cortisol) with acute HPA activity (as measured with salivary cortisol) in the same period, and (3) to determine which measure of HPA activity predicts anxiety and/or mediates the rearing/genotype influences on anxious behavior. Infant rhesus monkeys ( Macaca mulatta , N=61) were mother-peer-reared (MPR, n=21), peer-reared (PR, n=20), or surrogate-peer-reared (SPR, n=20) for 8 months, then all relocated into a large social housing situation for the next 18 months. Monkeys were genotyped for 5-HTT LPR and hair and saliva samples were collected for cortisol analysis at months 6, 12, 18, and 24. Behavior was recorded twice per week per subject from 2-24 months and analyzed for the duration of anxiety, social play, and grooming. Regression analysis established predictors of these behaviors. Rearing condition and sex were significant predictors of anxiety across the two years, and HPA activity added significant predictive power in the first six months only. Mediation of the rearing/anxiety relationship by the HPA axis was not evident. Interestingly, hair (but not salivary) cortisol early in life was positively correlated with later anxious behavior. These findings demonstrate the detrimental effects of adverse early life experience on behavioral development and shed light on the interplay between environment, adrenocortical activity, and anxiety. They further demonstrate the usefulness of a long-term measure of HPA activity in predicting later behavior.

A m-opioid receptor (OPRM1) single-nucleotide-polymorphism, found in both humans and rhesus macaques mediates the mother-infant attachment bond. Because mothers treat their sons and daughters differently, it is somewhat surprising that the role of infant sex has not been assessed in the context of a maternal-OPRM1-genotype-by-infant-sex interaction. The present study investigates the effect of maternal-OPRM1-genotype and infant sex on mother-infant behaviors. Over the first six months of offspring life, mother-infant behavioral data assessing attachment quality was collected twice weekly from a large number of rhesus monkey mother-infant pairs (N=161 dyads; n=64 female infants, n=97 male infants). Mothers were genotyped for OPRM1 variation. Factor analysis of the observed behaviors showed two factors: Attachment (maternal-infant cradling, rejections, and infant approaches and leaves), and Maternal Restraints (mother restrains infant, preventing exploration). Further analyses showed a two-way, maternal-genotype-by-infant-sex interaction for both factors. For Attachment, mothers with the CC genotype cradled and restrained (Maternal Restraints) their female infants more and rejected them less, when compared to female infants of CG mothers. Perhaps as a consequence, female infants of CC genotype mothers approached and left their mothers less often, when compared to female infants of CG mothers, likely an indication that female infants from mothers with CG genotype play a greater role in maintaining the mother-infant bond than do female infants from CC genotype mothers. This finding may also indicate a more secure attachment in infants from CC genotype mothers. Unlike female infants, on average, the mother-infant relationship of dyads with a male infant was largely undifferentiated by maternal genotype. These findings suggest that, in contrast to female infants from CG mothers, CC mothers and their female infants appear to have a closer mother-infant relationship which may portend close life-long bonds, as mothers and female offspring remain together throughout life. Male offspring appear to have a more aloof mother-infant bond regardless of OPRM1-genotype. The results of this study indicate that maternal-OPRM1 variation mediates mother-infant attachment behaviors for female infants and has less effect for male infants. This suggests that offspring sex should be included in studies investigating the effect of maternal-OPRM1 genotype on the mother-infant attachment relationship.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24830号 / 医博第4998号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 後藤, 慎平, 教授 河本, 宏, 教授 羽賀, 博典 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM