Rhesus macaques represent a valuable model in biomedical research and in development of vaccines and therapeutics. Due to the lack of reagents, the general properties of IgG and corresponding cellular receptors (FcγR) in this species are poorly characterized. We engineered recombinant IgGs containing each of the four rhesus macaque heavy constant region (CH) subclasses. To define FcγRs that mediate IgGs, we identified and characterized three FcγR classes, and generated recombinant cDNA constructs. cDNA IgH constructs were created by fusing – by sequence overlap extension PCRs – a gene segment encoding the murine variable heavy domain specific for the hapten NIP, an established specificity system for assessing antibody effector functions, with rhesus macaque CH fragments. The complete IgH constructs were transfected into J558L cells, a murine IgH-lost myeloma cell line expressing anti-NIP light chain. Secretion of engineered IgGs was determined by ELISAs using NIP-BSA and anti-monkey IgG-specific antibodies. Molecular cloning methods were applied to identify and clone FcγR genes, and recombinant FcγR cDNA constructs were created by the recombinant DNA method. Four engineered IgH cDNA constructs were successfully created. Recombinant IgGs, in the intact Ig form and retaining the original anti-NIP specificity, were successfully produced. Compared to those in humans, FcγRs in rhesus macaques share high homology, yet also feature a relatively high level of intra-species polymorphism and possess different N-linked glycosylation patterns. FcγR constructs and expression vectors were successfully generated. The chimeric recombinant IgGs are powerful tools for defining IgG functional properties and studying CH structure/function relationship. These molecules can also be used as immunogens for generation of antibodies capable of unequivocally detecting individual IgG subclasses. The findings on FcγRs validate rhesus macaques as a model for studying antibody responses, and underscore the need to take into account of the genetic heterogeneity. The FcγR constructs and vectors serve as a tool for further studies of IgG/FcγR interactions. We also reported here our findings from a separate study that the main female hormone, 17β-estradiol, is capable of restoring antibody responses to an influenza vaccine in a postmenopausal mouse model, suggesting that immunogenicity and efficacy of influenza vaccines should be evaluated in postmenopausal women.

<p>The ultimate goal of the nervous systems of all animals is conceptually simple: Manipulate the external environment to maximize one's own survival and reproduction. The myriad means animals employ in pursuit of this goal are astoundingly complex, but constrained by common factors. For example, to ensure survival, all animals must acquire the necessary nutrients to sustain metabolism. Similarly, social interaction of some form is necessary for mating and reproduction. For some animals, the required social interaction goes far beyond that necessary for mating. Humans and many other primates exist in complex social environments, the navigation of which are essential for adaptive behavior. This dissertation is concerned with processes of transforming sensory stimuli regarding both nutritive and social information into motor commands pursuant to the goals of survival and reproduction. Specifically, this dissertation deals with these processes in the rhesus macaque. Using a task in which monkeys make decisions simultaneously weighing outcomes of fruit juices and images of familiar conspecifics, I have examined the neurophysiology of social and nutritive factors as they contribute to choice behavior; with the ultimate goal of understanding how these disparate factors are weighed against each other and combined to produce coherent motor commands that result in adaptive social interactions and the successful procurement of resources. I began my investigation in the lateral intraparietal cortex, a well-studied area of the primate brain implicated in visual attention, oculomotor planning and control, and reward processing. My findings indicate the lateral intraparietal cortex represents social and nutritive reward information in a common neural currency. That is, the summed value of social and nutritive outcomes is proportional to the firing rates of parietal neurons. I continued my investigation in the striatum, a large and functionally diverse subcortical nuclei implicated in motor processing, reward processing and learning. Here I find a different pattern of results. Striatal neurons generally encoded information about either social outcome or juice rewards, but not both, with a medial or lateral bias in the location of social or juice information encoding neurons, respectively. In further contrast to the lateral intraparietal cortex, the firing rates of striatal neurons coding social and nutritive outcome information is heterogeneous and not directly related to the value of the outcome. This dissertation represents a few incremental steps toward understanding how social information and the drive toward social interaction are incorporated with other motivators to influence behavior. Understanding this process is a necessary step for elucidating, treating, and preventing pathologies</p> / Dissertation

Thesis (Ph. D.)--University of Washington, 2002. / Vita. Includes bibliographical references (p. 255-271).

Every waking moment, we make decisions, from where to move our eyes to what to eat for dinner. The ease and speed with which we do this belie the complexity of the underlying neuronal processing. In the visual system, every scene is processed via a complicated network of neurons that extends from the retina through multiple areas in the visual cortex. Each decision requires rapid coordination of signals from the relevant neurons. Deficits in this integration are likely causes of debilitating learning disorders, yet we know little about the processes involved. Previous studies of the macaque visual cortex indicate that as monkeys learn a new task the parts of the brain involved in decision making select which neurons they “listen to”: the most informative neurons become more strongly associated with the animal’s decisions as it learns. However, this process has only been studied over the course of several months as monkeys gradually learn a complex task. We set out to probe the dynamics of this relationship on a shorter timescale. We studied the middle temporal area (MT) of the visual cortex, where neurons are selective for binocular disparity (a depth cue) and motion direction; they have also been shown to contribute to perceptual decisions during motion- and depth-based tasks. After training monkeys on motion and depth detection tasks, we degraded the sensitivity of MT neurons for depth more than motion by reversibly inactivating two major inputs to MT—visual areas V2 and V3—by cooling. We hypothesized that degrading depth information more than motion would lead to bigger changes in the extent to which MT neurons contributed to decisions during the depth task than the motion task. We monitored this contribution to decisions, as measured by detect probability (DP), prior to and during daily inactivation sessions. We found that neuronal DP decreased during the depth task, indicating that neurons became less involved in these decisions. DP did not change during the motion task, suggesting that these changes can be specific to one feature. Our results revealed a level of fast, selective flexibility in the decision circuitry.

<p>The visual world is full of potentially important information, but only a subset of the world can be evaluated at any time. An essential function of the central nervous system is to rapidly and adaptively select which stimuli warrant attention. Much of the time, attention is directed towards stimuli that are relevant for current goals. However, things that have proven important in an organisms' personal or evolutionary past effectively compete with goal-relevant targets for attention. In humans, one example of this attentional superset is faces: faces attract attention even when they are in competition with immediate goals. Using a combination of behavioral, pharmacological, and electrophysiological techniques in the rhesus macaque, I investigated the physiological, neurobiological, and evolutionary determinants of the attentional capture of faces. First, I show that the prioritization of faces is evolutionarily conserved in primates. Face distractors also capture attention in rhesus macaques, a species of old world monkey, successfully competing with task goals for limited attentional resources. Importantly, the same classes of faces have the greatest attentional effects in both monkeys and humans. Further, I describe behavioral evidence that subcortical systems contribute to the attentional salience of faces in this species, proving an initial characterization of the neural mechanisms that may mediate this effect. Next, I examine the interaction between pupil size and vigilance for faces. A focal increase in luminance has long been known to provoke pupil constriction, but here I show that the pupil response to a flashed distractor is proportional to the allocation of attention to that image. Pupil constriction may provide a novel implicit metric of stimulus attention. In particular, face images provoked greater pupil constriction than non-face images. Moreover, I also find that baseline pupil size is a strong predictor of distractor interference, suggesting that arousal may modulate social vigilance. Therefore, I next examined the activity of single neurons within dorsal anterior cingulate cortex (dACC), a region implicated in task performance across a wide variety of tasks, but which also has strong connections to subcortical neuromodulatory centers responsible for regulating arousal. I find that the dACC discriminates between social and nonsocial distractors, scales with distractor attention, and predicts adjustments in arousal and vigilance state on upcoming trials. This is consistent with a model in which dACC supports task performance through regulating arousal. Finally, I turn to oxytocin (OT), a neuromodulatory hormone released during affiliative social interactions that is also implicated in regulating arousal. Though typically thought to generally enhance social attention, I report multiple circumstances in which OT suppresses, rather than enhances, vigilance for faces. This suggests a mechanism through which affiliative social interactions can reduce social vigilance, permitting more relaxed social interactions. Together, these results highlight an evolutionarily conserved neural circuit important for the adaptive, contextual modulation of reflexive face attention, a behavior that is compromised in both anxiety disorders and autism.</p> / Dissertation

Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 31-32).

abstract: In the past decade, research on the motor control side of neuroprosthetics has steadily gained momentum. However, modern research in prosthetic development supplements a focus on motor control with a concentration on sensory feedback. Simulating sensation is a central issue because without sensory capabilities, the sophistication of the most advanced motor control system fails to reach its full potential. This research is an effort toward the development of sensory feedback specifically for neuroprosthetic hands. The present aim of this work is to understand the processing and representation of cutaneous sensation by evaluating performance and neural activity in somatosensory cortex (SI) during a grasp task. A non-human primate (Macaca mulatta) was trained to reach out and grasp textured instrumented objects with a precision grip. Two different textures for the objects were used, 100% cotton cloth and 60-grade sandpaper, and the target object was presented at two different orientations. Of the 167 cells that were isolated for this experiment, only 42 were recorded while the subject executed a few blocks of successful trials for both textures. These latter cells were used in this study's statistical analysis. Of these, 37 units (88%) exhibited statistically significant task related activity. Twenty-two units (52%) exhibited statistically significant tuning to texture, and 16 units (38%) exhibited statistically significant tuning to posture. Ten of the cells (24%) exhibited statistically significant tuning to both texture and posture. These data suggest that single units in somatosensory cortex can encode multiple phenomena such as texture and posture. However, if this information is to be used to provide sensory feedback for a prosthesis, scientists must learn to further parse cortical activity to discover how to induce specific modalities of sensation. Future experiments should therefore be developed that probe more variables and that more systematically and comprehensively scan somatosensory cortex. This will allow researchers to seek out the existence or non-existence of cortical pockets reserved for certain modalities of sensation, which will be valuable in learning how to later provide appropriate sensory feedback for a prosthesis through cortical stimulation. / Dissertation/Thesis / M.S. Bioengineering 2011

Apes share a distinct set of morphological and anatomical characteristics that allow us to use our arms and hands in unique ways. Apes also have relatively larger brains with similar sulcal patterning indicating there is a distinctively hominoid brain structure. These features in great apes have consistently been linked with higher cognitive skills and are considered to be the precursors leading to the exceptional developments of humans over evolutionary time – establishing the physiological basis that allows us to make and use tools to modify our environments and build our unique cultures. This study examines the general model that orthogrady and suspensory postures were the antecedents for enhanced manipulative ability in apes, which consequently set the stage for enhanced cognitive abilities in early hominoids. The primary hypothesis is that if single-handed prehensility is enhanced by suspensory orthogrady, then we may predict ape feeding style will differ significantly from that of pronograde monkeys, allowing them to access foods in unique ways. Using sympatric white-handed gibbons, Hylobates lar, representative of orthograde apes, and pig-tailed macaques, Maccaca leonina, representative of pronograde monkeys, as models, the comparative feeding styles of primates were analyzed focusing on their positional behaviour and manual skill. Results support the hypothesis that gibbons exhibit a unique feeding style associated with their orthogrady/suspensory postures in comparison with pronograde macaques. This was demonstrated by their increased access to food in the trees with more stable postures, an expanded foraging radius, and more frequent use of the terminal branches, and was evident in their complex manipulative skills with larger manual repertoires, more variability in wrist use, and more sophisticated manual techniques. Moreover, significant differences in positional behaviour and manual skill demonstrated by gibbons and macaques were evident even when feeding on the same types of foods within their shared environment. This study proposes that the combined uniquely ape traits to forage in suspensory orthograde postures with precision dexterity have allowed apes to become highly selective feeders within their environments, leading to advance manual dexterity and cognitive prowess in apes.

No description available.

Prenatal stress has been correlated with adverse developmental outcomes affecting infant cognition and behavior. Previous studies have shown that prenatal stress can lead to increased susceptibility to adult disease but few studies have looked at the physiological stress response system by measuring the activity of the hypothalamicpituitary-adrenal (HPA) axis. Cortisol, the output of the HPA axis can be secreted in many different matrices (saliva, blood, urine, feces and hair). Most studies that do, only look at one measure of hormone production instead of examining multiple matrices. Additionally these studies do not look at the relationship between matrices. Hair provides a long-term assessment of cortisol hormone production as related to infant behavior. Four measures of cortisol representative of prenatal and postpartum periods were collected in a sample population of rhesus macaques at the NIH facility. No stress was applied to these animals and cortisol concentrations were assessed in maternal hair, infant hair, amniotic fluid, and mothers’ milk. These cortisol measures were then analyzed first to determine vii the relationships between the four measures and second to relate these cortisol values to infant behavior in the primate neonatal neurobehavioral assessment. Subjects of this study were 30 mothers and infants from the 2015 and 2016 breeding cohort. 25 of which, were unique dyads. Using four statistical analyses and 3 groupings of behavior, we found that maternal hair cortisol concentrations were correlated with different temperaments of infants, while milk cortisol concentrations were correlated with infant’s visual exploration of the environment. Additionally, an inverse relationship was found between hair cortisol concentrations and both hair cortisol concentrations with amniotic fluid cortisol. Together, the four statistical analyses show that Maternal HPA axis activation during and after pregnancy affects infant behavioral development 1 month postpartum.