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Non-human primates, especially rhesus macaques, have been a dominant model to study sensorimotor control of the upper limbs. Indeed, human and macaques have similar hands and homologous neural circuits to mediate manual behavior. However, few studies have systematically and quantitatively compared the manual behaviors of the two species. Such comparison is critical for assessing the validity of using the macaque sensorimotor system as a model of its human counterpart. In this study, we systematically compared the prehensile behaviors of humans and rhesus macaques using an identical experimental setup. We found human and macaque prehension kinematics to be generally similar with a few subtle differences. While the structure of the preshaping postures is similar in humans and macaques, human postures are more object-specific and human joints are less intercorrelated. Conversely, monkeys demonstrate more stereotypical grasping behaviors that are common across all grasp conditions and more variability in their postures across repeated grasps of the same object. Despite these subtle differences in manual behavior between humans and monkeys, our results bolster the use of the macaque model to understand the neural mechanisms of manual dexterity in humans.New and newsworthyMacaques have been a dominant animal model to study the neural mechanisms of human dexterity because they exhibit complex manual behavior. We show that the kinematics of prehension – a critical dexterous behavior – are largely similar in humans and macaques. However, human preshaping postures are more object-specific and the movement of human digits are less correlated with each other. The thumb, index, and wrist are major driver of these interspecies differences.

Correlated variability in neuronal activity (spike count correlations, rSC) can constrain how information is read out from populations of neurons. Traditionally, rSC is reported as a single value summarizing a brain area. However, single values, like summary statistics, stand to obscure underlying features of the constituent elements. We predict that in brain areas containing distinct neuronal subpopulations, different subpopulations will exhibit distinct levels of rSC that are not captured by the population rSC. We tested this idea in macaque superior colliculus (SC), a structure containing several functional classes (i.e., subpopulations) of neurons. We found that during saccade tasks, different functional classes exhibited differing degrees of rSC. “Delay class” neurons displayed the highest rSC, especially during saccades that relied on working memory. Such dependence of rSC on functional class and cognitive demand underscores the importance of taking functional subpopulations into account when attempting to model or infer population coding principles.

The macaque middle temporal (MT) area is well known for its visual motion selectivity and relevance to motion perception, but the possibility of it also reflecting higher-level cognitive functions has largely been ignored. We tested for effects of task performance distinct from sensory encoding by manipulating subjects' temporal evidence-weighting strategy during a direction discrimination task while performing electrophysiological recordings from groups of MT neurons in rhesus macaques (one male, one female). This revealed multiple components of MT responses that were, surprisingly, not interpretable as behaviorally relevant modulations of motion encoding, or as bottom-up consequences of the readout of motion direction from MT. The time-varying motion-driven responses of MT were strongly affected by our strategic manipulation—but with time courses opposite the subjects' temporal weighting strategies. Furthermore, large choice-correlated signals were represented in population activity distinct from its motion responses, with multiple phases that lagged psychophysical readout and even continued after the stimulus (but which preceded motor responses). In summary, a novel experimental manipulation of strategy allowed us to control the time course of readout to challenge the correlation between sensory responses and choices, and population-level analyses of simultaneously recorded ensembles allowed us to identify strong signals that were so distinct from direction encoding that conventional, single-neuron-centric analyses could not have revealed or properly characterized them. Together, these approaches revealed multiple cognitive contributions to MT responses that are task related but not functionally relevant to encoding or decoding of motion for psychophysical direction discrimination, providing a new perspective on the assumed status of MT as a simple sensory area.SIGNIFICANCE STATEMENTThis study extends understanding of the middle temporal (MT) area beyond its representation of visual motion. Combining multineuron recordings, population-level analyses, and controlled manipulation of task strategy, we exposed signals that depended on changes in temporal weighting strategy, but did not manifest as feedforward effects on behavior. This was demonstrated by (1) an inverse relationship between temporal dynamics of behavioral readout and sensory encoding, (2) a choice-correlated signal that always lagged the stimulus time points most correlated with decisions, and (3) a distinct choice-correlated signal after the stimulus. These findings invite re-evaluation of MT for functions outside of its established sensory role and highlight the power of experimenter-controlled changes in temporal strategy, coupled with recording and analysis approaches that transcend the single-neuron perspective.

Natural scenes are characterized by diverse image statistics, including various parameters of the luminance histogram, outputs of Gabor-like filters, and pairwise correlations between the filter outputs of different positions, orientations, and scales (Potilla-Simoncelli statistics). Some of these statistics capture the response properties of visual neurons. However, it remains unclear to what extent such statistics can explain neural responses to natural scenes and how neurons that are tuned to these statistics are distributed across the cortex. By using two-photon calcium imaging and an encoding-model approach, we addressed these issues in macaque visual areas V1 and V4. For each imaged neuron, we constructed an encoding model to mimic its responses to naturalistic videos. By extracting Potilla-Simoncelli statistics through outputs of both filters and filter correlations, and by computing an optimally weighted sum of these outputs, the model successfully reproduced responses in a subpopulation of neurons. We evaluated the selectivities of these neurons by quantifying the contributions of each statistic to visual responses. Neurons whose responses were mainly determined by Gabor-like filter outputs (low-level statistics) were abundant at most imaging sites in V1. In V4, the relative contribution of higher-order statistics, such as cross-scale correlation, was increased, and the neuronal selectivities varied markedly across sites; many sites included numerous neurons sensitive to luminance histogram parameters and/or correlation statistics, whereas some sites were dominated by neurons responding to low-level statistics. The results indicate that natural scene analysis progresses from V1 to V4, and neurons sharing preferred image statistics are locally clustered in V4.

Today, humans live in a world surrounded by electromagnetic fields. Numerous studies have been conducted to discover the biological, physiological, and behavioral effects of electromagnetic fields on humans and animals. Given the biological similarities between monkeys and humans, The present research aimed to examine Visual Memory (VM), hormonal, genomic, and anatomic changes, in the male rhesus macaques exposed to an Extremely Low-Frequency Magnetic Field (ELF-MF).Four male rhesus macaques (Macaca mulatta) were used. For the behavioral tests, the animals should be fasting for 17 hours. For the tests such as visual memory, the animal's cooperation was necessary. Using the radiation protocol, we exposed two monkeys to a 12-Hz electromagnetic field with a magnitude of 0.7 μT (electromagnetic radiation) four hours a day for a month. Before and after the exposure, a visual memory test was conducted using a coated device (visible reward) on a movable stand. Ten milliliters of blood was obtained from the femoral artery of each monkey, and half of it was used to examine cortisol serum levels using the MyBioSource kit (made in the USA). The other half of the blood was used to extract lymphocytes for assaying expressions of Glucocorticoid Receptor (GR) genes before and after radiation using the PCR method. Anatomic studies of the amygdala were carried out based on pre- and post-radiation Magnetic Resonance Imaging (MRI).Research results indicated that visual memory in male primates increased significantly after exposure to the 12-Hz frequency. Hormonal analysis at the 12-Hz frequency showed a decrease in cortisol serum levels. However, visual memory and serum cortisol levels did not change considerably in male primates in the control group. There was no considerable amygdala volumetric difference after exposure to the 12-Hz frequency. The expression of the GR genes decreased in the 12-Hz group compared to the control group.In short, these results indicated that ELF might benefit memory enhancement because exposure to the 12-HZ ELF can enhance visual memory. This outcome may be due to a decrease in plasma cortisol and or expression of GR genes. Moreover, direct amygdala involvement in this regard cannot be recommended.The effects of Extremely Low-Frequency Electromagnetic Fields (ELF-EMF) of 12 Hz on monkeys were studied.The results showed a reduction in the serum cortisol levels and the expression of GR genes.The amygdala anatomical area changes were not significant in the experimental group.In the experimental group, visual memory (delay of 30- and 60-s evaluation) improved after exposure to a frequency of 12 Hz.Extremely low-frequency electromagnetic fields are among the most important factors affecting humans. This study aimed to determine the fields of 12-Hz frequency on the visual memory changes of male monkeys. The importance of research is due to the cognitive similarity of monkeys to humans. The findings of the research can be attributed to humans. Behavioral, hormonal, genetic, and anatomical studies indicated improvement in visual memory (test monkeys versus control monkeys). This study demonstrates the effect of the 12-Hz frequency on the monkey's visual memory. Researchers can study 12-Hz frequency in other cognitive indices.

The programmable nuclease technology CRISPR-Cas9 has revolutionized gene editing in the last decade. Due to the risk of off-target editing, accurate and sensitive methods for off-target characterization are crucial prior to applying CRISPR-Cas9 therapeutically. Here, we utilized a rhesus macaque model to compare the predictive values of CIRCLE-seq, an in vitro off-target prediction method, with in silico prediction (ISP) based solely on genomic sequence comparisons. We use AmpliSeq HD error-corrected sequencing to validate off-target sites predicted by CIRCLE-seq and ISP for a CD33 guide RNA (gRNA) with thousands of off-target sites predicted by ISP and CIRCLE-seq. We found poor correlation between the sites predicted by the two methods. When almost 500 sites predicted by each method were analyzed by error-corrected sequencing of hematopoietic cells following transplantation, 19 off-target sites revealed insertion or deletion mutations. Of these sites, 8 were predicted by both methods, 8 by CIRCLE-seq only, and 3 by ISP only. The levels of cells with these off-target edits exhibited no expansion or abnormal behavior in vivo in animals followed for up to 2 years. In addition, we utilized an unbiased method termed CAST-seq to search for translocations between the on-target site and off-target sites present in animals following transplantation, detecting one specific translocation that persisted in blood cells for at least 1 year following transplantation. In conclusion, neither CIRCLE-seq or ISP predicted all sites, and a combination of careful gRNA design, followed by screening for predicted off-target sites in target cells by multiple methods, may be required for optimizing safety of clinical development.

To decipher the organizational logic of complex brain circuits, it is important to chart long-distance pathways while preserving micron-level accuracy of local network. However, mapping the neuronal projections with individual-axon resolution in the large and complex primate brain is still challenging. Herein, we describe a highly efficient pipeline for three-dimensional mapping of the entire macaque brain with subcellular resolution. The pipeline includes a novel poly-N-acryloyl glycinamide (PNAGA)-based embedding method for long-term structure and fluorescence preservation, high-resolution and rapid whole-brain optical imaging, and image post-processing. The cytoarchitectonic information of the entire macaque brain was acquired with a voxel size of 0.32 μm × 0.32 μm × 10 μm, showing its anatomical structure with cell distribution, density, and shape. Furthermore, thanks to viral labeling, individual long-distance projection axons from the frontal cortex were for the first time reconstructed across the entire brain hemisphere with a voxel size of 0.65 μm × 0.65 μm × 3 μm. Our results show that individual cortical axons originating from the prefrontal cortex simultaneously target multiple brain regions, including the visual cortex, striatum, thalamus, and midbrain. This pipeline provides an efficient method for cellular and circuitry investigation of the whole macaque brain with individual-axon resolution, and can shed light on brain function and disorders.

The testis produces gametes through spermatogenesis and evolves rapidly at both the morphological and molecular level in mammals1-6, probably owing to the evolutionary pressure on males to be reproductively successful7. However, the molecular evolution of individual spermatogenic cell types across mammals remains largely uncharacterized. Here we report evolutionary analyses of single-nucleus transcriptome data for testes from 11 species that cover the three main mammalian lineages (eutherians, marsupials and monotremes) and birds (the evolutionary outgroup), and include seven primates. We find that the rapid evolution of the testis was driven by accelerated fixation rates of gene expression changes, amino acid substitutions and new genes in late spermatogenic stages, probably facilitated by reduced pleiotropic constraints, haploid selection and transcriptionally permissive chromatin. We identify temporal expression changes of individual genes across species and conserved expression programs controlling ancestral spermatogenic processes. Genes predominantly expressed in spermatogonia (germ cells fuelling spermatogenesis) and Sertoli (somatic support) cells accumulated on X chromosomes during evolution, presumably owing to male-beneficial selective forces. Further work identified transcriptomal differences between X- and Y-bearing spermatids and uncovered that meiotic sex-chromosome inactivation (MSCI) also occurs in monotremes and hence is common to mammalian sex-chromosome systems. Thus, the mechanism of meiotic silencing of unsynapsed chromatin, which underlies MSCI, is an ancestral mammalian feature. Our study illuminates the molecular evolution of spermatogenesis and associated selective forces, and provides a resource for investigating the biology of the testis across mammals. We thank all members of the Kaessmann group, S. Tirier for discussions and N. Trost for the administration of the Kaessmann laboratory server. Computations were performed on the Kaessmann laboratory server and the bwForCluster from the Heidelberg University Computational Center (supported by the state of Baden-Württemberg through bwHPC and the German Research Foundation grant no. INST 35/1134-1 FUGG). This research was supported by grants from the ERC (grant no. 615253, OntoTransEvol) and German Research Council (DFG, grant nos. SFB 873 and KA 1710/4-1) to H.K., by the CellNetworks Postdoc Fellowship and EMBO Long-Term Fellowship to F.M. (grant no. ALTF 591-2017), and by the Australian Research Council (grant no. FT160100267) to F.G. and by the Novo Nordisk Foundation (grant no. NNF21OC0069913) to K.A. and (grant no. NNF18OC0031004) to M.H.S. The use of all other mammalian samples for the type of work described in this study was approved by ERC ethics screening panels (ERC starting grant no. 242597, SexGenTransEvolution and ERC consolidator grant no. 615253, OntoTransEvol).

Food supply is one of the major drivers of animal behavior, and the gut microbiome is an important mediator between food supply and its effects on physiology. However, predicting the outcome of diet change on microbiome and consequences for the animal has proven extremely challenging. We propose this reflects processes occurring at different scales. Inadequate accounting for the multi-level complexity of nutrition (nutrients, foods, diets) obscures the diet influence on microbiome and subsequently animal. Here, we present a detailed year-round, multi-level analysis of diet and microbiome changes in a wild population of a temperate primate, the rhesus macaque (Macaca mulatta). Total daily food and nutrient intake of 6 male and 6 female macaques was monitored in each of the 4 seasons (total 120 days observations). For each individual, we found significant variation in the microbiome between all 4 seasons. This response was more strongly correlated with changes in macronutrient intake than with food items and much of the response could be explained at the level of 6 ecological guilds-sets of taxa sharing similar responses to nutrient intake. We conclude that study of diet, microbiome, and animal performance in ecology will more effectively identify patterns if diet is recorded at the level of nutrient intake. Although microbiome response to diet does show variation in species-level taxa in response to food items, there is greater commonality in response at the level of guilds. A goal for microbiome researchers should be to identify genes encoding microbial attributes that can define such guilds.

Sequence learning is a ubiquitous facet of human and animal cognition. Here, using a common sequence reproduction task, we investigated whether and how the ordinal and relational structures linking consecutive elements are acquired by human adults, children, and macaque monkeys. While children and monkeys exhibited significantly lower precision than adults for spatial location and temporal order information, only monkeys appeared to exceedingly focus on the first item. Most importantly, only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used a chunking strategy to compress sequences in working memory. Monkeys did not detect such relational structures, even after extensive training. Monkey behavior was captured by a conjunctive coding model, whereas a chunk-based conjunctive model explained more variance in humans. These age- and species-related differences are indicative of developmental and evolutionary mechanisms of sequence encoding and may provide novel insights into the uniquely human cognitive capacities.SIGNIFICANCE STATEMENTSequence learning, the ability to encode the order of discrete elements and their relationships presented within a sequence, is a ubiquitous facet of cognition among humans and animals. By exploring sequence-processing abilities at different human developmental stages and in nonhuman primates, we found that only humans, regardless of age, spontaneously extracted the spatial relations between consecutive items and used an internal language to compress sequences in working memory. The findings provided insights into understanding the origins of sequence capabilities in humans and how they evolve through development to identify the unique aspects of human cognitive capacity, which includes the comprehension, learning, and production of sequences, and perhaps, above all, language processing.

During the past century, macaque bioresources have provided remarkable scientific and biomedical discoveries related to the understanding of human physiology, neuroanatomy, reproduction, development, cognition, and pathology. Considerable progress has been made, and an urgent need has arisen to develop infrastructure and viable settings to meet the current global demand in research models during the so-called new normal after COVID-19 era. This review highlights the critical need for macaque bioresources and proposes the establishment of a designated primate research center to integrate research in primate laboratories for the rescue and rehabilitation of wild macaques. Key areas where macaque models have been and continue to be essential for advancing fundamental knowledge in biomedical and biological research are outlined. Detailed genetic studies on macaque bioresources of Thai origin can further facilitate the rapid pace of vaccine discovery.

Group living is a source of stress and an individuals��� social environment has been shown to have a significant effect on its health and well-being. However, little is known about how different social organizations affect the stress levels of their members. Is living in a hierarchical society more or less stressful than living in a more tolerant structure? Here, we assess cortisol concentrations in the hair of two macaque species with radically different dominance styles: the egalitarian Tonkean macaque (Macaca Tonkeana) and the despotic long-tailed macaques (Macaca fascicularis). Hair was sampled in winter and again in late spring in two mixed-sex groups of 22 Tonkean macaques and 9 long-tailed macaques; Hair cortisol concentrations were significantly higher in the egalitarian Tonkean macaques than in the despotic long-tailed macaques, ranging from 161.13 to 938.8 pg/mg (mean �� SD 349.67 �� 126.22) and from 134.46 to 339.86 pg/mg (mean �� SD 231.2 �� 44.24), respectively. There was no difference between male and female cortisol concentrations, but hair cortisol increased with age in males. Dominance rank certainty was lower among female Tonkean macaques compared to long-tailed macaques. Our results suggest that species differences in dominance styles may translate into differences in long-term cortisol concentrations. We suggest that the higher cortisol concentrations in Tonkean macaques could be linked to the instability and lack of predictability and control around social relationships. Being part of a social group can be very stressful, depending on the social structure of this group. We found that the more socially tolerant Tonkean macaques exhibited on average higher hair cortisol concentrations than more despotic long-tailed macaques. Males and females exhibited similar concentrations of hair cortisol in both species, but in male Tonkean macaques concentrations increased with age. The finding that overall cortisol levels were higher in the more tolerant species suggests that psychological arousal due to unpredictable social relations and mating competition may be an important driver of cortisol release in this species despite its overall tolerant social organization.

What is the effect of prior experience on sensorimotor behavior? We studied the following intriguing behavior: monkeys fixating a small target direct their gaze above the target if the background is dark. Fixating a target once on a bright background, then on a dark background, yields 2 gaze directions, typically one above the other; hence the name, ‘dark-background-contingent upshift of gaze', which is abbreviated as ‘upshift’. Is the upshift only an attempt to avoid using the fovea in the dark? If it is, we might expect to also observe a downshift and a sideshift. We studied gaze direction in a large group of 10 rhesus monkeys from Tubingen, to which we added published data from 4 cynomolgus monkeys from Rehovot. The upshift was ubiquitous, and there was no systematic sideshift. What is the function of the upshift? Is it related to vision in the dark? Here, we concentrate on the effect of the monkeys’ previous training. Seven of the 14 monkeys were accustomed to working in the dark (‘dark-habituated’), while the other 7 had worked in bright ambient light (‘bright-habituated’). The main result of this study is that the dark-habituated monkeys had a much larger upshift: the mean upshift was 2.2° in the dark-habituated monkeys, versus 0.5° in the bright-habituated. Thus, the upshift depends on habituation; the size of the upshift reflects months-long cumulative experience. These findings suggest that the function of the upshift is indeed related to seeing in the dark.

We conduct a comparative evaluation of the visual systems from the retina to the muscles of the mouse and the macaque monkey noting the differences and similarities between these two species. The topics covered include (1) visual-field overlap, (2) visual spatial resolution, (3) V1 cortical point-image [i.e., V1 tissue dedicated to analyzing a unit receptive field], (4) object versus motion encoding, (5) oculomotor range, (6) eye, head, and body movement coordination, and (7) neocortical and cerebellar function. We also discuss blindsight in rodents and primates which provides insights on how the neocortex mediates conscious vision in these species. This review is timely because the field of visuomotor neurophysiology is expanding beyond the macaque monkey to include the mouse; there is therefore a need for a comparative analysis between these two species on how the brain generates visuomotor responses.

Anthropogenic land-use changes increase the frequency of interactions and habitat overlap between humans and macaques which play an important role in zoonotic disease transmission. This exploratory qualitative study aimed to examine connections between land-use change and macaque-human interactions and assess the chance of zoonotic disease transmission. We conducted ethnographic interviews and focus group discussions in Old Dhaka, Madaripur, and Chandpur, Bangladesh. Participants reported significant anthropogenic landscape transformations leading to increased human-macaque contact in the study areas. Participants also reported that all three sites underwent substantial landscape alteration from natural or agricultural land to a human-altered environment with roads, commercial, and residential buildings. Participants noted that the disappearance of forestland appeared to increase the macaque dependence on backyard fruit trees. Where rivers and ponds were filled to support local construction, macaques were also observed as becoming more dependent upon human water sources. These changed may help expanding the macaques' foraging areas, and they appear to be invading new areas where people are not culturally habituated to living with them. In response, many residents reported reacting aggressively toward the macaques, which they believed led to more bites and scratches. However, other respondents accepted the presence of macaques around their homes. Few participants considered macaques to be a source of disease transmission. This study revealed that local environmental changes, deforestation, urban expansion, construction, and water bodies' disappearance are linked to increasing human-macaque interactions. Understanding these interactions is critical to develop successful mitigation interventions at interfaces with a high risk for viral disease spillover.

Contains fulltext : 239140.pdf (Publisher’s version ) (Open Access) The triple-network model of psychopathology is a framework to explain the functional and structural neuroimaging phenotypes of psychiatric and neurological disorders. It describes the interactions within and between three distributed networks: the salience, default-mode, and central executive networks. These have been associated with brain disorder traits in patients. Homologous networks have been proposed in animal models, but their integration into a triple-network organization has not yet been determined. Using resting-state datasets, we demonstrate conserved spatio-temporal properties between triple-network elements in human, macaque, and mouse. The model predictions were also shown to apply in a mouse model for depression. To validate spatial homologies, we developed a data-driven approach to convert mouse brain maps into human standard coordinates. Finally, using high-resolution viral tracers in the mouse, we refined an anatomical model for these networks and validated this using optogenetics in mice and tractography in humans. Unexpectedly, we find serotonin involvement within the salience rather than the default-mode network. Our results support the existence of a triple-network system in the mouse that shares properties with that of humans along several dimensions, including a disease condition. Finally, we demonstrate a method to humanize mouse brain networks that opens doors to fully data-driven trans-species comparisons. 8 p.

Objective Antibody-dependent enhancement (ADE) affects host-virus dynamics in fundamentally different ways: i) enhancement of initial virus acquisition, and/or ii) increased disease progression/severity. Here we address the question whether anti-HIV-1 antibodies can enhance initial infection. While cell-culture experiments hinted at this possibility, in-vivo proof remained elusive. Design We used passive immunization in nonhuman primates challenged with simian-human immunodeficiency virus (SHIV), a chimera expressing HIV-1 envelope. We purified IgG from rhesus monkeys with early-stage SHIV infection - before cross-neutralizing anti-HIV-1 antibodies had developed - and screened for maximal complement-mediated antibody-dependent enhancement (C'-ADE) of viral replication with a SHIV strain phylogenetically distinct from that harbored by IgG donor macaques. IgG fractions with maximal C'-ADE but lacking neutralization were combined to yield enhancing anti-SHIV IgG (enSHIVIG). Results We serially enrolled naive macaques (Group 1) to determine the minimal and 50% animal infectious doses required to establish persistent infection after intrarectal SHIV challenge. The first animal was inoculated with a 1:10 virus-stock dilution; after this animal's viral RNA load was >104copies/ml, the next macaque was challenged with 10x less virus, a process repeated until viremia no longer ensued. Group 2 was pretreated intravenously with enSHIVIG 24 hours before SHIV challenge. Overall, Group 2 macaques required 3.4-fold less virus compared to controls (p = 0.002). This finding is consistent with enhanced susceptibility of the passively immunized animals to mucosal SHIV challenge. Conclusion These passive immunization data give proof of IgG-mediated enhanced virus acquisition after mucosal exposure - a potential concern for antibody-based AIDS vaccine development.

In the field of biomedicine, instance segmentation / individualization is important in analyzing the number, the morphology and the distribution of neurons for the whole slide images. Traditionally, biologists apply stereology technique to manually count the number of neurons in the regions of interest and estimate the number in anatomical regions or the entire brain. This is very tedious and time-consuming. In this paper, we propose a multiscale fully convolutional regression neural network combined with competitive region growing technique to individualize size-varying and touching neurons in major anatomical regions of macaque brain. Given that neuron instance or contour annotations are infeasible to obtain in certain regions, such as dentate gyrus where thousands of touching neurons are present, we ask expert to perform point annotations in the center location of neurons (noted as neuron centroids) for training. Thanks to the multiscale resolution achieved by parallel multiple receptive fields and different network depths, our proposed network succeeds in detecting the centroids of size-varying and touching neurons. Competitive region growing is then applied on these centroids to achieve neuron instance segmentation. Experiments on macaque brain data suggest that our proposed method outperform the state-of-the-art methods in terms of neuron instance segmentation performance. To our knowledge, this is the first deep learning research work to individualize size-varying and touching neurons only using point annotations in major anatomical regions in the macaque brain. The cartographic representation of the number and the average orientation of neurons illustrates the synthesis of multi-gigabyte image information in the form of cartography, and shows the characteristics of different anatomical regions from mesoscopic level.

Primates are popular species in wildlife tourism contexts and provide economic benefits to habitat countries where primate-based tourism activities are a part of the country’s tourism economy. Primate tourism runs a broad gamut from safari-like expeditions within remote primate habitats to designated monkey parks and incidental primate tourism. In most forms of primate tourism, primate ecology and behaviour are directly influenced by humans, making these interfaces particularly relevant for examination using the lens of ethnoprimatology. While several studies have assessed the impact of tourism on primates, little is known about people’s motivations for observing monkeys for recreational purposes. Here we present two case studies—the Jigokudani Monkey Park, Japan, and the Telaga Warna Nature Recreational Park, Indonesia—where we provide quantitative assessments of people’s motivations for visiting managed (monkey parks) and unmanaged (incidental) monkey tourism sites. We further show that management regimes, socio-demographic attributes, previous experience of interactions with macaques, and feeding them play a role in people’s desire to visit macaque tourism sites. In Japan, those who had interacted with macaques before were more likely to visit the park to observe macaques clearly and at close quarters. In contrast, respondents in Indonesia were more interested in the recreational opportunities offered by the nature reserve rather than in macaques. However, here too, people who had interacted with macaques earlier were more likely to visit incidental macaque tourist sites for the sole purpose of viewing or interacting with macaques. Almost 50% of the Japanese respondents visited the monkey park due to personal inclinations, while less than 14% of people in Indonesia visited the park of their own volition. Also, over 57% of the Japanese respondents said that visiting monkey parks helped them gain a better understanding of macaque behaviour, whereas only about 26% respondents said likewise in Indonesia. Unlike the Japanese respondents, most of the Indonesian respondents engaged in feeding macaques. These findings suggest that management regimes as well as socio-demographic attributes may influence people’s motivations to visit macaque tourism sites.

Concurrent genetic neuromodulation and functional magnetic resonance imaging (fMRI) in primates has provided a valuable opportunity to assess the modified brain-wide operation in the resting state. However, its application to link the network operation with behavior still remains challenging. Here, we combined chemogenetic silencing of the primary somatosensory cortex (SI) with tactile fMRI and related behaviors in macaques. Focal chemogenetic silencing of functionally identified SI hand region impaired grasping behavior. The same silencing also attenuated hand stimulation-evoked fMRI signal at both the local silencing site and the anatomically and/or functionally connected downstream grasping network, suggesting altered network operation underlying the induced behavioral impairment. Furthermore, the hand region silencing unexpectedly disinhibited foot representation with accompanying behavioral hypersensitization. These results demonstrate that focal chemogenetic silencing with sensory fMRI in macaques unveils bidirectional network changes to generate multifaceted behavioral impairments, thereby opening a pivotal window toward elucidating the causal network operation underpinning higher brain functions in primates., 手と足の感覚は、実は脳の中でつながっていた --脳障害による活動変化の広がりを見ることで常識を覆す発見、脳機能・疾患機序の理解へ前進--. 京都大学プレスリリース. 2021-10-21.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne RNA virus prevalent in Asia, Europe, and Africa, and can cause a hemorrhagic disease (CCHF) in humans with mortality rates as high as 60%. A general lack of both effective medical countermeasures and a comprehensive understanding of disease pathogenesis is partly driven by an historical lack of viable CCHF animal models. Recently, a cynomolgous macaque model of CCHF disease was developed. Here, we document the targeted transcriptomic response of non-human primates (NHP) to two different CCHFV strains; Afghan09-2990 and Kosova Hoti that both yielded a mild CCHF disease state. We utilized a targeted gene panel to elucidate the transcriptomic changes occurring in NHP whole blood during CCHFV infection; a first for any primate species. We show numerous upregulated genes starting at 1 day post-challenge through 14 days post-challenge. Early gene changes fell predominantly in the interferon stimulated gene family with later gene changes coinciding with an adaptive immune response to the virus. There are subtle differences between viral strains, namely duration of the differentially expressed gene response and biological pathways enriched. After recovery, NHPs showed no lasting transcriptomic changes at the end of sample collection.

Lethal gang attacks, in which multiple aggressors attack a single victim, are among the most widespread forms of violence between human groups. Gang attacks are also frequent in some other social mammals, such as chimpanzees (Pan troglodytes), wolves (Canis lupus), spotted hyaenas (Crocuta crocuta), and meerkats (Suricata suricatta). So far, species where gang attacks have been observed share one or more of these socio-ecological features: territoriality, fission-fusion, cooperative breeding or coalitionary bonds. However, the scarcity of data in other taxa makes it challenging to determine if one/all of these socio-ecological features are necessary and sufficient to drive the evolution of gang attacks. Here we describe the first-ever reports of intergroup gang attacks in the crested macaque, using data on three groups collected over 13 years, with the joint observation times for the three groups summing up to 37 years. Crested macaques gang attacked outgroup conspecifics when aggressors were numerically superior to victims. Adult females were the most frequent age/sex category to attack outgroup conspecifics. The victims were mostly adult females, and infants. We propose that coalitionary bonds, hostility towards outgroup individuals, and the ability to estimate numerical odds may suffice to trigger intergroup gang attacks when the conditions favour an imbalance of power between victims and attackers.

Individuals’ spatial position is affected by social factors. The majority of studies correlating spatial position and social factors have used methods with drawbacks. A more complete method was developed by Dolado & Beltran (2011) in captive animals. The present study aimed to apply a modified version of this method in two semi-free-ranging macaque groups. The proposed method divides group’s surroundings into different subareas, selecting different points in each subarea and calculating the coordinates of these points. We filmed each group and analyzed the videos using an activated time transition recording to determine the individuals’ coordinates. With these data, we calculated spatial variables, allowing us to obtain groups’ spatial patterns. The current method improves on previous procedures and could be applied to larger study areas and groups than the method of Dolado & Beltran (2011), thus representing a viable option for studying spatial distribution patterns in semi-free-ranging macaque groups.

The dorsal visual stream, the cortical circuit that in the primate brain is mainly dedicated to the visual control of actions, is split into two routes, a lateral and a medial one, both involved in coding different aspects of sensorimotor control of actions. The lateral route, named “lateral grasping network”, is mainly involved in the control of the distal part of prehension, namely grasping and manipulation. The medial route, named “reach-to-grasp network”, is involved in the control of the full deployment of prehension act, from the direction of arm movement to the shaping of the hand according to the object to be grasped. In macaque monkeys, the reach-to-grasp network (the target of this review) includes areas of the superior parietal lobule (SPL) that hosts visual and somatosensory neurons well suited to control goal-directed limb movements toward stationary as well as moving objects. After a brief summary of the neuronal functional properties of these areas, we will analyze their cortical and thalamic inputs thanks to retrograde neuronal tracers separately injected into the SPL areas V6, V6A, PEc, and PE. These areas receive visual and somatosensory information distributed in a caudorostral, visuosomatic trend, and some of them are directly connected with the dorsal premotor cortex. This review is particularly focused on the origin and type of visual information reaching the SPL, and on the functional role this information can play in guiding limb interaction with objects in structured and dynamic environments.

Frontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.Significant StatementFrontoparietal networks contribute to many cognitive functions in humans and macaques, but little is known about the organization of frontoparietal networks in the New World common marmoset monkey. Here, we investigated the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. These frontoparietal connection showed overarching pattern of interareal organization consistent with Old world monkeys. These findings demonstrate parallel frontoparietal processing streams in marmosets.

Self-amplifying mRNA (saRNA) represents a promising platform for nucleic acid delivery of vaccine immunogens. Unlike plasmid DNA, saRNA does not require entry into the nucleus of target cells for expression, having the capacity to drive higher protein expression compared to mRNA as it replicates within the cytoplasm. In this study, we examined the potential of stabilized native-like HIV-1 Envelope glycoprotein (Env) trimers to elicit immune responses when delivered by saRNA polyplexes (PLXs), assembled with linear polyethylenimine. We showed that Venezuelan equine encephalitis virus (VEEV) saRNA induces a stronger humoral immune response to the encoded transgene compared to Semliki Forest virus saRNA. Moreover, we characterized the immunogenicity of the soluble and membrane-bound ConSOSL.UFO Env design in mice and showed a faster humoral kinetic and an immunoglobulin G (IgG)2a skew using a membrane-bound design. The immune response generated by PLX VEEV saRNA encoding the membrane-bound Env was then evaluated in larger animal models including macaques, in which low doses induced high IgG responses. Our data demonstrated that the VEEV saRNA PLX nanoparticle formulation represents a suitable platform for the delivery of stabilized HIV-1 Env and has the potential to be used in a variety of vaccine regimens., Graphical abstract, Aldon, McKay, and colleagues evaluated the potential of formulated VEEV and SFV self-amplifying mRNA (saRNA) for the delivery of HIV-1 Env stabilized trimers. The authors demonstrate great potential for PEI-polyplex formulated VEEV-saRNA platform, which elicits strong humoral responses at low doses in non-human primates.

To perform real-world tasks like grasping, the primate brain has to process visual object information so that the grip aperture can be adjusted before contact with the object is made. Previous studies have demonstrated that the posterior subsector of the Anterior Intraparietal area (pAIP) is connected to frontal area 45B, and the anterior subsector of AIP (aAIP) to F5a (Premereur et al., 2015). However, the role of area 45B and F5a in visually-guided object grasping is poorly understood. Here, we investigated the role of area 45B, F5a and F5p in visually-guided grasping. If a neuronal response to an object during passive fixation represents the activation of a motor command related to the preshaping of the hand, such neurons should prefer objects presented within reachable distance. Conversely, neurons encoding a pure visual representation of an object should be less affected by viewing distance. Contrary to our expectations, we found that the majority of neurons in area 45B were object- and viewing distance selective, with a clear preference for the near viewing distance. Area F5a showed much weaker object selectivity compared to 45B, with a similar preference for objects presented at the Near position emerging mainly in the late epoch. Finally, F5p neurons were less object selective and frequently preferred objects presented at the Far position. Therefore, contrary to our expectations, neurons in area 45B – but not F5p neurons – prefer objects presented in peripersonal space.Significance statementThe current experiment provides the first evidence on the neural representation of distance in frontal areas that are active during visually-guided grasping. Area 45B and F5a neurons were object- and distance-selective, and preferred the near viewing distance even for objects with identical retinal size. In area F5p we observed strong visual responses with an unexpected preference for the Far viewing distance, suggesting that the motor-related object representation was still active during the presentation of objects outside reaching distance.

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal recordings and behavior. Guided by anatomical MRI, we recorded single-cell activity in parietal area PFG during passive fixation of real-world objects. Overall, we observed a pronounced, long-lasting and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons exhibiting periods of hyperexcitability during the recovery phase. We applied the same stimulation protocol during visually-guided grasping of objects, and observed a significant grasping impairment. These results provide the first experimental evidence on the effects of cTBS on single neurons in awake behaving monkeys.

Optogenetic methods have been widely used in rodent brains, but remain relatively under-developed for nonhuman primates such as rhesus macaques, an animal model with a large brain expressing sophisticated sensory, motor and cognitive behaviors. To address challenges in behavioral optogenetics in large brains, we developed Opto-Array, a chronically implantable array of light-emitting diodes for high-throughput optogenetic perturbation. We demonstrated that optogenetic silencing in the macaque primary visual cortex with the help of the Opto-Array results in reliable retinotopic visual deficits in a luminance discrimination task. We separately confirmed that Opto-Array illumination results in local neural silencing, and that behavioral effects are not due to tissue heating. These results demonstrate the effectiveness of the Opto-Array for behavioral optogenetic applications in large brains. An implantable array of LEDs called the Opto-Array facilitates optogenetic manipulations in the nonhuman primate brain.

Human-modified landscapes play an important role in supporting the survival of primate populations, but they may also facilitate human–primate interactions, possibly leading to negative outcomes. We conducted a scalar investigation of the role of landscape structure in shaping the intensity of crop feeding by a generalist primate species, the rhesus macaque (Macaca mulatta) in northern India. At the species level, we used behavioral sampling techniques to assess habitat selection by two groups of rhesus macaques. At the landscape level, we used GIS-based analyses to quantify landscape structure in terms of class-level and patch-level metrics and correlated it with macaque crop feeding intensities. We found that, on average, both study groups spent only 15% of their total feeding time on cultivars. However, they spent a large proportion of their feeding (BH: 75% and CH: 36%) and ranging (BH: 72% and CH: 39%) time in agroecosystem habitats. Landscape level analysis showed that crop feeding intensity was not related to total area under cultivation. Instead, macaque crop feeding intensity was positively correlated to the arrangement of deciduous forest patches beside cultivated area patches. Our findings call for careful appraisal of landscape management practices as a potential mitigation strategy for primate crop-depredation in such human-modified landscapes.

Speciation and hybridization are intertwined processes in the study of evolution. Hybridization between sufficiently diverged populations can result in genomic conflict within offspring, causing reduced viability and fertility, thus increasing divergence between populations. Conflicts between mitochondrial and nuclear genes are increasingly found to play a role in this process in various systems. We examine the possibility of this conflict in the bear macaque, Macaca arctoides (Primates: Cercopithecidae), a primate species exhibiting mitonuclear discordance due to extensive hybridization with species in the sinica and fascicularis groups. Here, divergence, introgression and natural selection of mitonuclear genes (N = 160) relative to nuclear control genes (N = 144) were analysed to determine whether there are evolutionary processes involved in resolving the potential conflict caused by mitonuclear discordance. Nucleotide divergence of mitonuclear genes is increased relative to control nuclear genes between M. arctoides and the species sharing its nuclear ancestry (p = 0.007), consistent with genetic conflict. However, measures of introgression and selection do not identify large-scale co-introgression or co-evolution as means to resolve mitonuclear conflict. Nonetheless, mitochondrial tRNA synthetases stand out in analyses using dN/dS and extended branch lengths as potential targets of selection. The methodology implemented provides a framework that can be used to examine the effects of mitonuclear co-introgression and co-evolution on a genomic scale in a variety of systems.

In 1991, Felleman and Van Essen published their seminal study regarding hierarchical processing in the primate cerebral cortex. Their work encompassed a widescale analysis of connections reported through tracing between 35 regions in the macaque visual cortex, extending from cortical regions to the laminar level. In this work, we revisit laminar-level connectivity in the macaque brain using a whole-brain MRI-based approach. We use multi-modal ex-vivo MRI imaging of the macaque brain in both white and grey matter, which are then integrated via a simple model of laminar connectivity. This model uses a granularity-based approach to define a set of rules that expands cortical connections to the laminar level. Different fiber tracking routines are then examined in order to explore the ability of our model to infer laminar connectivity. The network of macaque cortical laminar connectivity resulting from the chosen routine is then validated in the visual cortex by comparison to findings from Felleman and Van Essen with an 83% accuracy level. By using a more comprehensive definition of the cortex that addresses its heterogenous laminar composition, we can explore a new avenue of structural connectivity on the laminar level.

An ordered relation of structure and function has been a cornerstone in thinking about brain organization. Like the brain itself, however, this is not straightforward and is confounded both by functional intricacy and structural plasticity (many routes to a given outcome). As a striking case of putative structure–function correlation, this mini-review focuses on the relatively well-characterized pattern of cytochrome oxidase (CO) blobs (aka “patches” or “puffs”) in the supragranular layers of macaque monkey visual cortex. The pattern is without doubt visually compelling, and the semi-dichotomous array of CO+ blobs and CO− interblobs is consistent with multiple studies reporting compartment-specific preferential connectivity and distinctive physiological response properties. Nevertheless, as briefly reviewed here, the finer anatomical organization of this system is surprisingly under-investigated, and the relation to functional aspects, therefore, unclear. Microcircuitry, cell type, and three-dimensional spatiotemporal level investigations of the CO+ CO− pattern are needed and may open new views to structure–function organization of visual cortex, and to phylogenetic and ontogenetic comparisons across nonhuman primates (NHP), and between NHP and humans.

BACKGROUND Assessment of pain in macaques is challenging. The aims of this study were (1) to investigate current knowledge and attitudes of primate veterinarians concerning acute pain in macaques; (2) to synthesise current knowledge and opinion to facilitate pain assessment. A primary question of interest was whether more confident individuals differ in their knowledge and attitudes from less-confident individuals. METHODS An online survey was conducted amongst primate veterinarians serving both laboratories and zoos/sanctuaries. The questionnaire consisted of demographic information, attitudes towards pain, pain rating and analgesics, pain recognition and confidence in recognising pain and sources of information used. RESULTS AND CONCLUSIONS There was generally good use of analgesia by respondents. More confident individuals reported that they recognise pain both behaviourally and in facial expressions, rated all pain signs more highly and used more analgesics. Specialist support networks aimed at increasing veterinarian confidence in macaque pain assessment could be beneficial.

In mammals, the placenta mediates maternal–fetal nutrient and waste exchange and acts in an immunomodulatory way to facilitate maternal–fetal tolerance. The placenta is highly diverse across mammalian species, yet the molecular mechanisms that distinguish the placenta of human from other mammals are not fully understood. Using an interspecies transcriptomic comparison of human, macaque, and mouse late-gestation placentae, we identified hundreds of genes with lineage-specific expression—including dozens that are placentally enriched and potentially related to pregnancy. We further annotated the enhancers for different human tissues using epigenomic data and demonstrate that the placenta and chorion are unique in that their enhancers display the least conservation. We identified numerous lineage-specific human placental enhancers and found they highly overlap with specific families of endogenous retroviruses (ERVs), including MER21A, MER41A/B, and MER39B that were previously linked to immune response and placental function. Among these ERV families, we further demonstrate that MER41A/B insertions create dozens of lineage-specific serum response factor-binding loci in human, including one adjacent to FBN2, a placenta-specific gene with increased expression in humans that produces the peptide hormone placensin to stimulate glucose secretion and trophoblast invasion. Overall, our results demonstrate the prevalence of lineage-specific placental enhancers which are frequently associated with ERV insertions and likely facilitate the lineage-specific evolution of the mammalian placenta.

KEY POINTS Neurons in the posterior superior temporal polysensory area (STPp) showed significant directional selectivity in response to vestibular, optic flow and combined visual-vestibular stimuli. By comparison to the dorsal medial superior temporal area, the visual latency was slower in STPp but the vestibular latency was faster. Heading preferences under combined stimulation in STPp were usually dominated by visual signals. Cross-modal enhancement was observed in STPp when both vestibular and visual cues were presented together at their heading preferences. ABSTRACT Human neuroimaging data implicated that the superior temporal polysensory area (STP) might be involved in vestibular-visual interaction during heading computations, but the heading selectivity has not been examined in the macaque. Here, we investigated the convergence of optic flow and vestibular signals in macaque STP by using a virtual-reality system and found that 6.3% of STP neurons showed multisensory responses, with visual and vestibular direction preferences either congruent or opposite in roughly equal proportion. The percentage of vestibular-tuned cells (18.3%) was much smaller than that of visual-tuned cells (30.4%) in STP. The vestibular tuning strength was usually weaker than the visual condition. The visual latency was significantly slower in STPp than in the dorsal medial superior temporal area (MSTd), but the vestibular latency was significantly faster than in MSTd. During the bimodal condition, STP cells' response was dominated by visual signals, with the visual heading preference not affected by the vestibular signals but the response amplitudes modulated by vestibular signals in a subadditive way.

In the current study, we examined the number, distribution, and aspects of the neurochemical identities of infracortical white matter neurons, also termed white matter interstitial cells (WMICs), in the brains of a southern lesser galago (Galago moholi), a black-capped squirrel monkey (Saimiri boliviensis boliviensis), and a crested macaque (Macaca nigra). Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most dense close to inner cortical border, decreasing in density with depth in the white matter. Stereological analysis of NeuN-immunopositive cells revealed estimates of approximately 1.1, 10.8, and 37.7 million WMICs within the infracortical white matter of the galago, squirrel monkey, and crested macaque, respectively. The total numbers of WMICs form a distinct negative allometric relationship with brain mass and white matter volume when examined in a larger sample of primates where similar measures have been obtained. In all three primates studied, the highest densities of WMICs were in the white matter of the frontal lobe, with the occipital lobe having the lowest. Immunostaining revealed significant subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS) and calretinin, with very few WMICs containing parvalbumin, and none containing calbindin. The nNOS and calretinin immunopositive WMICs represent approximately 21% of the total WMIC population; however, variances in the proportions of these neurochemical phenotypes were noted. Our results indicate that both the squirrel monkey and crested macaque might be informative animal models for the study of WMICs in neurodegenerative and psychiatric disorders in humans.

Background:. Deep brain stimulation (DBS) has seizure-suppressing effects but the molecular mechanisms underlying its therapeutic action remain unclear. This study aimed to systematically elucidate the mechanisms underlying DBS-induced seizure suppression at a molecular level. Methods:. We established a macaque model of mesial temporal lobe epilepsy (mTLE), and continuous high-frequency hippocampus DBS (hip-DBS) was applied for 3 months. The effects of hip-DBS on hippocampus gene expression were examined using high-throughput microarray analysis followed by bioinformatics analysis. Moreover, the microarray results were validated using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. Results:. The results showed that chronic hip-DBS modulated the hippocampal gene expression. We identified 4119 differentially expressed genes and assigned these genes to 16 model profiles. Series test of cluster analysis showed that profiles 5, 3, and 2 were the predominant expression profiles. Moreover, profile 5 was mainly involved in focal adhesion and extracellular matrix-receptor interaction pathway. Nine dysregulated genes (Arhgap5, Col1a2, Itgb1, Pik3r1, Lama4, Fn1, Col3a1, Itga9, and Shc4) and three genes (Col1a2, Itgb1, and Flna) in these two pathways were further validated by qRT-PCR and Western blot analyses, respectively, which showed a concordance. Conclusion:. Our findings suggest that hip-DBS could markedly reverse mTLE-induced abnormal gene expression. Findings from this study establish the basis for further investigation of the underlying regulatory mechanisms of DBS for mTLE.

Blindsight is the residual visuo-motor ability without subjective awareness observed after lesions of the primary visual cortex (V1). Various visual functions are retained, however, instrumental visual associative learning remains to be investigated. Here we examined the secondary reinforcing properties of visual cues presented to the hemianopic field of macaque monkeys with unilateral V1 lesions. Our aim was to test the potential role of visual pathways bypassing V1 in reinforcing visual instrumental learning. When learning the location of a hidden area in an oculomotor search task, conditioned visual cues presented to the lesion-affected hemifield operated as an effective secondary reinforcer. We noted that not only the hidden area location, but also the vector of the saccade entering the target area was reinforced. Importantly, when the visual reinforcement signal was presented in the lesion-affected field, the monkeys continued searching, as opposed to stopping when the cue was presented in the intact field. This suggests the monkeys were less confident that the target location had been discovered when the reinforcement cue was presented in the affected field. These results indicate that the visual signals mediated by the residual visual pathways after V1 lesions can access fundamental reinforcement mechanisms but with impaired visual, 盲視マカクサルは視覚意識が無くても自発的行動を学習できる. 京都大学プレスリリース. 2021-09-14., Using visual information to learn voluntary behavior while blind. 京都大学プレスリリース. 2021-09-14.

In non-human primates, at the junction of the prefrontal with the premotor cortex, there is a sector designated as frontal eye field (FEF), involved in controlling oculomotor behavior and spatial attention. Evidence for at least two FEFs in humans is at the basis of the still open issue of the possible homologies between the macaque and the human frontal oculomotor system. In this review article we address this issue suggesting a new view solidly grounded on evidence from the last decade showing that, in macaques, the FEF is at the core of an oculomotor domain in which several distinct areas, including areas 45A and 45B, provide the substrate for parallel processing of different aspects of oculomotor behavior. Based on comparative considerations, we will propose a correspondence between some of the macaque and the human oculomotor fields, thus suggesting sharing of neural substrate for oculomotor control, gaze processing, and orienting attention in space. Accordingly, this article could contribute to settle some aspects of the so-called "enigma" of the human FEF anatomy.

Emerging appreciation for the hyperdirect pathway (HDP) as an important cortical glutamatergic input to the subthalamic nucleus (STN) has motivated a wide range of recent investigations on its role in motor control, as well as the mechanisms of subthalamic deep brain stimulation (DBS). However, the pathway anatomy and terminal arbor morphometry by which the HDP links cortical and subthalamic activity are incompletely understood. One critical hindrance to advancing understanding is the lack of anatomically detailed population models which can help explain how HDP pathway anatomy and neuronal biophysics give rise to spatiotemporal patterns of stimulus-response activity observed in vivo. Therefore, the goal of this study was to establish a population model of motor HDP axons through application of generative algorithms constrained by recent histology and imaging data. The products of this effort include a de novo macaque brain atlas, detailed statistical analysis of histological reconstructions of macaque motor HDP axons, and the generation of 10,000 morphometrically constrained synthetic motor HDP axons. The synthetic HDP axons exhibited a 3.8% mean error with respect to parametric distributions of the fiber target volume, total length, number of bifurcations, bifurcation angles, meander angles, and segment lengths measured in BDA-labeled HDP axon reconstructions. As such, this large population of synthetic motor HDP axons represents an anatomically based foundation for biophysical simulations that can be coupled to electrophysiological and/or behavioral measurements, with the goal of better understanding the role of the HDP in motor system activity.

Primates are group-living creatures that constantly face the challenges posed by complex social demands. To date, the cortical mechanisms underlying social information processing have been the major focus of attention. However, emerging evidence suggests that subcortical regions also mediate the collection and processing of information from other agents. Here, we review the literature supporting the hypothesis that behavioral variables important for decision-making, i.e., stimulus, action, and outcome, are associated with agent information (self and other) in subcortical regions, such as the amygdala, striatum, lateral hypothalamus, and dopaminergic midbrain nuclei. Such self-relevant and other-relevant associative signals are then integrated into a social utility signal, presumably at the level of midbrain dopamine neurons. This social utility signal allows decision makers to organize their optimal behavior in accordance with social demands. Determining how self-relevant and other-relevant signals might be altered in psychiatric and neurodevelopmental disorders will be fundamental to better understand how social behaviors are dysregulated in disease conditions.

[Aim] Understanding patterns and processes of geographic genetic variation within and among closely related species is the essence of phylogeography. Japanese macaques, also called snow monkeys, have been extensively studied, particularly in the fields of sociobiology, ecology and experimental biology; however, our knowledge of their evolutionary history is relatively limited. In this study we aimed to elucidate the geographic patterns of genetic variation in Japanese macaques and the processes that underlie them. [Location] Japan. [Taxa] Japanese macaque, Macaca fuscata; rhesus macaque, M. mulatta; Taiwanese macaque, M. cyclopis. [Methods] Double-digest restriction site-associated DNA (RAD) sequencing was used to identify genome-wide single nucleotide variants. We used fineRADstructure, ADMIXTURE and principal component analyses to estimate the genetic population structure. Phylogenetic relationships were then inferred based on neighbour-net, neighbour-joining, maximum likelihood and SVDquartets algorithms. We assessed gene flow using demographic inference and ABBA-BABA tests, and estimated past distributions during the Last Glacial Maximum (LGM) using ecological niche modelling. [Results] Japanese macaques show a sister group relationship with a clade comprising Chinese rhesus, Indian rhesus and Taiwanese macaques. Japanese macaques comprise major north-eastern and south-western clades, with a boundary located near central Japan, and gene flow between the north-eastern and south-western lineages was detected. Refugia during the LGM were estimated to be distributed in limited areas along the south coasts of the Japanese archipelago. [Main conclusions] Phylogeographic variation of Japanese macaques is likely due mainly to northeast–southwest divergence, which resulted from withdrawal into refugia during the glacial period, and subsequent gene flow.

Reward valuation in social contexts is by nature relative rather than absolute; it is made in reference to others. This socially relative reward valuation is based on our propensity to conduct comparisons and competitions between self and other. Exploring its neural substrate has been an active area of research in human neuroimaging. More recently, electrophysiological investigation of the macaque brain has enabled us to understand neural mechanisms underlying this valuation process at single-neuron and network levels. Here I show that shared neural networks centered at the medial prefrontal cortex and dopamine-related subcortical regions are involved in this process in humans and nonhuman primates. Thus, socially relative reward valuation is mediated by cortico-subcortically coordinated activity linking social and reward brain networks.

Brain signal recordings with epidural microarrays constitute a low-invasive approach for recording distributed neuronal signals. Epidural field potentials (EFPs) may serve as a safe and highly beneficial signal source for a variety of research questions arising from both basic and applied neuroscience. A wider use of these signals, however, is constrained by a lack of data on their specific information content. Here, we make use of the high spatial resolution and the columnar organization of macaque primary visual cortex (V1) to investigate whether and to what extent EFP signals preserve information about various visual stimulus features. Two monkeys were presented with different feature combinations of location, size, shape, and color, yielding a total of 375 stimulus conditions. Visual features were chosen to access different spatial levels of functional organization. We found that, besides being highly specific for locational information, EFPs were significantly modulated by small differences in size, shape, and color, allowing for high stimulus classification rates even at the single-trial level. The results support the notion that EFPs constitute a low-invasive, highly beneficial signal source for longer-term recordings for medical and basic research by showing that they convey detailed and reliable information about constituent features of activating stimuli., Fischer and Wegener demonstrated that epidural field potentials in the macaque primary visual cortex can provide detailed information about non-spatial visual object features. Specifically, they revealed that these low-invasive measurements conveyed information about the processing of different visual stimuli features such as location, size, shape, and color.

Key points Responses to natural scenes are the business of the retina. We find primate ganglion cell responses to such scenes consistent with those to simpler stimuli. A biophysical model confirmed this and predicted ganglion cell responses with close-to-retinal reliability. Primate ganglion cell responses to natural scenes were driven by temporal variations in color and luminance over the receptive field center caused by eye movements, and little influenced by interaction of center and surround with structure in the scene. We discuss implications in the context of efficient coding of the visual environment. Much information in a higher spatiotemporal frequency band is concentrated in the magnocellular pathway. Abstract Responses of visual neurons to natural scenes provide a link between classical descriptions of receptive field structure and visual perception of the natural environment. A natural scene video with a movement pattern resembling that of primate eye movements was used to evoke responses from macaque ganglion cells. Cell responses were well described through known properties of cell receptive fields. Different analyses converge to show that responses primarily derive from the temporal pattern of stimulation derived from eye movements, rather than spatial receptive field structure beyond center size and position. This was confirmed using a model that predicted ganglion cell responses close to retinal reliability, with only a small contribution of the surround relative to the center. We also found that the spatiotemporal spectrum of the stimulus is modified in ganglion cell responses, and this can reduce redundancy in the retinal signal. This is more pronounced in the magnocellular pathway, which is much better suited to transmit the detailed structure of natural scenes than the parvocellular pathway. Whitening is less important for chromatic channels. Taken together, this shows how a complex interplay across space, time and spectral content sculpts ganglion cell responses. This article is protected by copyright. All rights reserved.

Invasive tract-tracing studies in rodents implicate a direct connection between the subiculum and bed nucleus of the stria terminalis (BNST) as a key component of neural pathways mediating hippocampal regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. A clear characterisation of the connections linking the subiculum and BNST in humans and non-human primates is lacking. To address this, we first delineated the projections from the subiculum to the BNST using anterograde tracers injected into macaque monkeys, revealing evidence for a monosynaptic subiculum-BNST projection involving the fornix. Second, we used in vivo diffusion MRI tractography in macaques and humans to demonstrate substantial subiculum complex connectivity to the BNST in both species. This connection was primarily mediated through the fornix, with additional connectivity via the amygdala, consistent with rodent anatomy. Third, utilising the twin-based nature of our human sample, we found that microstructural properties of these tracts are moderately heritable (h2 ∼ 0.5). In a final analysis, we found no evidence of any significant association between subiculum complex-BNST tract microstructure and indices of perceived stress/dispositional negativity and alcohol use, derived from principal component analysis decomposition of self-report data. We did, however, find subiculum complex-BNST tract microstructure associations with BMI, age, and sex. Our findings address a key translational gap in our knowledge of the neurocircuitry regulating stress.

Cholesterol-25-hydroxylase (CH25H) and its enzymatic product 25-hydroxycholesterol (25HC) exert broadly antiviral activity including inhibiting HIV-1 infection. However, their antiviral immunity and therapeutic efficacy in a nonhuman primate model are unknown. Here, we report that the regimen of 25HC combined with antiretroviral therapy (ART), provides profound immunological modulation towards inhibiting viral replication in chronically SIVmac239-infected rhesus macaques (RMs). Compared to the ART alone, this regimen more effectively controlled SIV replication, enhanced SIV-specific cellular immune responses, restored the ratio of CD4/CD8 cells, reversed the hyperactivation state of CD4+ T cells, and inhibited the secretion of proinflammatory cytokines by CD4+ and CD8+ T lymphocytes in chronically SIV-infected RMs. Furthermore, the in vivo safety and the preliminary pharmacokinetics of the 25HC compound were assessed in this RM model. Taken together, these assessments help explain the profound relationship between cholesterol metabolism, immune modulation, and antiviral activities by 25HC. These results provide insight for developing novel therapeutic drug candidates against HIV-1 infection and other related diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s12250-021-00407-6.

The pulvinar is the largest nucleus in the primate thalamus and has topographically organized connections with multiple cortical areas, thereby forming extensive cortico-pulvino-cortical input-output loops. Neurophysiological studies have suggested a role for these transthalamic pathways in regulating information transmission between cortical areas. However, evidence for a causal role of the pulvinar in regulating cortico-cortical interactions is sparse and it is not known whether pulvinar's influences on cortical networks are task-dependent or, alternatively, reflect more basic large-scale network properties that maintain functional connectivity across networks regardless of active task demands. In the current study, under passive viewing conditions, we conducted simultaneous electrophysiological recordings from ventral (area V4) and dorsal (lateral intraparietal area [LIP]) nodes of macaque visual system, while reversibly inactivating the dorsal part of the lateral pulvinar (dPL), which shares common anatomical connectivity with V4 and LIP, to probe a causal role of the pulvinar. Our results show a significant reduction in local field potential phase coherence between LIP and V4 in low frequencies (4-15 Hz) following muscimol injection into dPL. At the local level, no significant changes in firing rates or LFP power were observed in LIP or in V4 following dPL inactivation. Synchronization between pulvinar spikes and cortical LFP phase decreased in low frequencies (4-15 Hz) both in LIP and V4, while the low frequency synchronization between LIP spikes and pulvinar phase increased. These results indicate a causal role for pulvinar in synchronizing neural activity between interconnected cortical nodes of a large-scale network, even in the absence of an active task state.

The projections from the claustrum to cortical areas within and adjacent to the superior parietal lobule were studied in 10 macaque monkeys, using retrograde tracers, computerized reconstructions, and quantitative methods. In contrast with the classical view that posterior parietal areas receive afferents primarily from the dorsal and posterior regions of the claustrum, we found that these areas receive more extensive projections, including substantial afferents from the anterior and ventral regions of the claustrum. Moreover, our findings uncover a previously unsuspected variability in the precise regions of the claustrum that originate the projections, according to the target areas. For example, areas dominated by somatosensory inputs for control of body movements tend to receive most afferents from the dorsal-posterior claustrum, whereas those which also receive significant visual inputs tend to receive more afferents from the ventral claustrum. In addition, different areas within these broadly defined groups differ in terms of quantitative emphasis in the origin of projections. Overall, these results argue against a simple model whereby adjacency in the cortex determines adjacency in the sectors of claustral origin of projections and indicate that subnetworks defined by commonality of function may be an important factor in defining claustrocortical topography.