Showing papers on "Primate published in 2022"

Cell transcriptomic atlas of the non-human primate Macaca fascicularis

Abstract: Studying tissue composition and function in non-human primates (NHPs) is crucial to understand the nature of our own species. Here we present a large-scale cell transcriptomic atlas that encompasses over 1 million cells from 45 tissues of the adult NHP Macaca fascicularis. This dataset provides a vast annotated resource to study a species phylogenetically close to humans. To demonstrate the utility of the atlas, we have reconstructed the cell-cell interaction networks that drive Wnt signalling across the body, mapped the distribution of receptors and co-receptors for viruses causing human infectious diseases, and intersected our data with human genetic disease orthologues to establish potential clinical associations. Our M. fascicularis cell atlas constitutes an essential reference for future studies in humans and NHPs.

The development and evolution of inhibitory neurons in primate cerebrum

Abstract: Abstract Neuroanatomists have long speculated that expanded primate brains contain an increased morphological diversity of inhibitory neurons (INs) 1 , and recent studies have identified primate-specific neuronal populations at the molecular level 2 . However, we know little about the developmental mechanisms that specify evolutionarily novel cell types in the brain. Here, we reconstruct gene expression trajectories specifying INs generated throughout the neurogenic period in macaques and mice by analysing the transcriptomes of 250,181 cells. We find that the initial classes of INs generated prenatally are largely conserved among mammals. Nonetheless, we identify two contrasting developmental mechanisms for specifying evolutionarily novel cell types during prenatal development. First, we show that recently identified primate-specific TAC3 striatal INs are specified by a unique transcriptional programme in progenitors followed by induction of a distinct suite of neuropeptides and neurotransmitter receptors in new-born neurons. Second, we find that multiple classes of transcriptionally conserved olfactory bulb (OB)-bound precursors are redirected to expanded primate white matter and striatum. These classes include a novel peristriatal class of striatum laureatum neurons that resemble dopaminergic periglomerular cells of the OB. We propose an evolutionary model in which conserved initial classes of neurons supplying the smaller primate OB are reused in the enlarged striatum and cortex. Together, our results provide a unified developmental taxonomy of initial classes of mammalian INs and reveal multiple developmental mechanisms for neural cell type evolution.

Molecular and cellular evolution of the primate dorsolateral prefrontal cortex

Abstract: The granular dorsolateral prefrontal cortex (dlPFC) is an evolutionary specialization of primates that is centrally involved in cognition. We assessed more than 600,000 single-nucleus transcriptomes from adult human, chimpanzee, macaque, and marmoset dlPFC. Although most cell subtypes defined transcriptomically are conserved, we detected several that exist only in a subset of species as well as substantial species-specific molecular differences across homologous neuronal, glial, and non-neural subtypes. The latter are exemplified by human-specific switching between expression of the neuropeptide somatostatin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine production in certain interneurons. The above molecular differences are also illustrated by expression of the neuropsychiatric risk gene FOXP2, which is human-specific in microglia and primate-specific in layer 4 granular neurons. We generated a comprehensive survey of the dlPFC cellular repertoire and its shared and divergent features in anthropoid primates. Description Primate brain diversity Primate brains benefit from an evolutionary specialization of the cortex that supports cognition. Ma et al. tracked transcriptomes from cellular nuclei sampled from human, chimpanzee, macaque, and marmoset brain cortices. The transcriptomes define groups of cell types, some of which are conserved and some that differ between these species. Several human-specific specializations were identified. Expression patterns of more than 900 genes associated with brain disorders revealed a variety of conserved, divergent, group-specific patterns. —PJH Single-cell transcriptomics reveals prefrontal cell taxonomy and species differences in human, chimpanzee, macaque, and marmoset. INTRODUCTION The dorsolateral prefrontal cortex (dlPFC) lies at the center of high-order cognition and complex social behaviors, which are highly derived traits in anthropoid primates—particularly in humans. RATIONALE The granular dlPFC represents an evolutionary specialization found only in anthropoid primates, and alterations in the molecular and cellular mechanisms underlying its intricate circuitry have been implicated in myriad neuropsychiatric diseases. However, little is known about the full repertoire of cell types in the primate dlPFC and how conserved these cell types are between human and other primate species. RESULTS We generated single-nucleus transcriptome data profiling more than 600,000 nuclei from the dlPFC of adult humans, chimpanzees, rhesus macaques, and common marmosets, thus spanning major primate phylogenetic groups. To study regulatory mechanisms underlying human-specific divergence, we generated single-nucleus multiome data (snATAC-seq and snRNA-seq) profiling the human dlPFC. Through cell clustering, marker gene expression, and integration with published multimodal and multispecies data we defined three levels of hierarchically organized taxonomy of transcriptomically defined neuronal, glial, and non-neural cell types in the four species, including four major cell classes, 29 subclasses and 114 subtypes. Most cell subtypes were conserved across the four species but we unraveled prominent species differences both at the molecular and cellular levels. We identified five cell subtypes detected in only a subset of species, including a layer (L) 2-3 intratelencephalic subtype absent in marmosets, an inhibitory neuron subtype exclusive to marmosets, and a microglial subtype detected only in humans. Cross-species comparisons of cell type proportions showed that L2-3 intratelencephalic neurons underwent substantial expansion in humans compared with other species as well as in Catarrhini as compared with marmosets. Gene expression entropy analysis revealed more transcriptomic heterogeneity among L2-3 intratelencephalic neurons in Catarrhini compared to marmosets. These results confirm and extend theories of primate cortical expansion. Within homologous cell subtypes across species, we identified prominent molecular changes. These are characterized by loss of expression of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine (including dopamine) biosynthesis, in the inhibitory neurons of chimpanzees that are homologous to TH-expressing inhibitory neurons in the other species studied. Among TH-expressing homologous cell subtypes in humans, macaques, and marmosets, we identified a human-specific posttranscriptional switch between the neuropeptide SST and TH, and the human-specific expression of genes involved in dopaminergic function. Through transcriptomic comparisons across the four primate species and immunohistochemistry across 51 mammal species, we found that the neuropsychiatric risk gene FOXP2 exhibited human-specific expression in microglia and primate-specific expression in L4 excitatory neurons. By integrating chromatin accessibility and gene coexpression, we identified cis-regulatory elements regulating FOXP2 expression and constructed FOXP2 regulatory networks including downstream targets mirroring the cell type- and species-specific FOXP2 expression patterns. CONCLUSION We produced a transcriptomic catalog of the primate dlPFC cell types, complemented with epigenomic characterization in the human dlPFC. Our analyses delineated cell type homology and transcriptomic conservation across species and identified species divergence at the molecular and cellular levels, as well as potential epigenomic mechanisms underlying these differences. Shared and species-divergent features were implicated in biological pathways and neuropsychiatric diseases. Our data may serve as a resource for future studies on prefrontal cortex function and disease. Transcriptomic taxonomy of the dlPFC in four anthropoid primates. (Top left) Homologous regions of the dlPFC dissected for snRNA-seq and sn-multiome analyses. (Top right) 114 hierarchically organized (dendrogram) transcriptomically defined cell subtypes distributed across the four species (bar plots; same color code as in the top left panel), with species-specific variations highlighted. (Bottom) Notable molecular changes across species featured by species-specific FOXP2 expression and the human-specific posttranscriptional switching between SST and TH.

Global importance of Indigenous Peoples, their lands, and knowledge systems for saving the world’s primates from extinction

Abstract: Primates, represented by 521 species, are distributed across 91 countries primarily in the Neotropic, Afrotropic, and Indo-Malayan realms. Primates inhabit a wide range of habitats and play critical roles in sustaining healthy ecosystems that benefit human and nonhuman communities. Approximately 68% of primate species are threatened with extinction because of global pressures to convert their habitats for agricultural production and the extraction of natural resources. Here, we review the scientific literature and conduct a spatial analysis to assess the significance of Indigenous Peoples’ lands in safeguarding primate biodiversity. We found that Indigenous Peoples’ lands account for 30% of the primate range, and 71% of primate species inhabit these lands. As their range on these lands increases, primate species are less likely to be classified as threatened or have declining populations. Safeguarding Indigenous Peoples’ lands, languages, and cultures represents our greatest chance to prevent the extinction of the world’s primates.

The language void 10 years on: multimodal primate communication research is still uncommon

Abstract: Human language is thought to have evolved from non-linguistic communication systems present in the primate lineage. Scientists rely on data from extant primate species to estimate how this happened, with debates centering around which modality (vocalization, gesture, facial expression) was a likely precursor. In 2011, we demonstrated that different theoretical and methodological approaches are used to collect data about each modality, rendering datasets incomplete and comparisons problematic. Here, 10 years later, we conducted a follow-up systematic review to test whether patterns have changed, examining the primate communication literature published between 2011 and 2020. In sum, despite the promising progress in addressing some gaps in our knowledge, systematic biases still exist and multimodal research remains uncommon. We argue that theories of language evolution are unlikely to advance until the field of primate communication research acknowledges and rectifies the gaps in our knowledge.

Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate

Abstract: Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Social connections predict brain structure in a multidimensional free-ranging primate society

Abstract: Reproduction and survival in most primate species reflects management of both competitive and cooperative relationships. Here, we investigated the links between neuroanatomy and sociality in free-ranging rhesus macaques. In adults, the number of social partners predicted the volume of the mid–superior temporal sulcus and ventral-dysgranular insula, implicated in social decision-making and empathy, respectively. We found no link between brain structure and other key social variables such as social status or indirect connectedness in adults, nor between maternal social networks or status and dependent infant brain structure. Our findings demonstrate that the size of specific brain structures varies with the number of direct affiliative social connections and suggest that this relationship may arise during development. These results reinforce proposed links between social network size, biological success, and the expansion of specific brain circuits.

A convergent interaction engine: vocal communication among marmoset monkeys

Abstract: To understand the primate origins of the human interaction engine, it is worthwhile to focus not only on great apes but also on callitrichid monkeys (marmosets and tamarins). Like humans, but unlike great apes, callitrichids are cooperative breeders, and thus habitually engage in coordinated joint actions, for instance when an infant is handed over from one group member to another. We first explore the hypothesis that these habitual cooperative interactions, the marmoset interactional ethology, are supported by the same key elements as found in the human interaction engine: mutual gaze (during joint action), turn-taking, volubility, as well as group-wide prosociality and trust. Marmosets show clear evidence of these features. We next examine the prediction that, if such an interaction engine can indeed give rise to more flexible communication, callitrichids may also possess elaborate communicative skills. A review of marmoset vocal communication confirms unusual abilities in these small primates: high volubility and large vocal repertoires, vocal learning and babbling in immatures, and voluntary usage and control. We end by discussing how the adoption of cooperative breeding during human evolution may have catalysed language evolution by adding these convergent consequences to the great ape-like cognitive system of our hominin ancestors. This article is part of the theme issue ‘Revisiting the human ‘interaction engine’: comparative approaches to social action coordination’.

Redefining varicose projection astrocytes in primates

Abstract: Varicose projection astrocytes (VP-As) are found in the cerebral cortex and have been described to be specific to humans and chimpanzees. To further examine the phylogenetic distribution of this cell type, we analyzed cortical tissue from several primates ranging from primitive primates to primates evolutionary closer to human such as apes. We specifically analyzed tissue from four strepsirrhine species, one tarsier, six species of platyrrhine monkeys, ten species of cercopithecoid monkeys, two hylobatid ape species, four to six cases each of chimpanzee, bonobo, gorilla, and orangutan, and thirteen human. We found that VP-As were present only in human and other apes (hominoids) and were absent in all other species. We showed that VP-As are localized to layer VI and the superficial white matter of the cortex. The presence of VP-As co-occured with interlaminar astrocytes that also had varicosities in their processes. Due to their location, their long tangential processes, and their irregular presence within species, we propose that VP-As are astrocytes that develop varicosities under specific conditions and that are not a distinct astrocyte type.

Evolutionarily conservative and non-conservative regulatory networks during primate interneuron development revealed by single-cell RNA and ATAC sequencing

Abstract: The differences in size and function between primate and rodent brains, and the association of disturbed excitatory/inhibitory balance with many neurodevelopmental disorders highlight the importance to study primate ganglionic eminences (GEs) development. Here we used single-cell RNA and ATAC sequencing to characterize the emergence of cell diversity in monkey and human GEs where most striatal and cortical interneurons are generated. We identified regional and temporal diversity among progenitor cells which give rise to a variety of interneurons. These cells are specified within the primate GEs by well conserved gene regulatory networks, similar to those identified in mice. However, we detected, in human, several novel regulatory pathways or factors involved in the specification and migration of interneurons. Importantly, comparison of progenitors between our human and published mouse GE datasets led to the discovery and confirmation of outer radial glial cells in GEs in human cortex. Our findings reveal both evolutionarily conservative and nonconservative regulatory networks in primate GEs, which may contribute to their larger brain sizes and more complex neural networks compared with mouse.

Female reproductive aging in seven primate species: Patterns and consequences

Abstract: Age-related changes in fertility have increasingly been documented in wild animal populations: In many species the youngest and oldest reproducers are disadvantaged relative to prime adults. How do these effects evolve, and what explains their diversity across species? Tackling this question requires detailed data on patterns of age-related reproductive performance in multiple animal species. Here, we compare patterns and consequences of age-related changes in female reproductive performance in seven primate populations that have been subjects of long-term continuous study for 29 to 57 y. We document evidence of age effects on fertility and on offspring performance in most, but not all, of these primate species. Specifically, females of six species showed longer interbirth intervals in the oldest age classes, youngest age classes, or both, and the oldest females also showed relatively fewer completed interbirth intervals. In addition, five species showed markedly lower survival among offspring born to the oldest mothers, and two species showed reduced survival for offspring born to both the youngest and the oldest mothers. In contrast, we found mixed evidence that maternal age affects the age at which daughters first reproduce: Only in muriquis and to some extent in chimpanzees, the only two species with female-biased dispersal, did relatively young mothers produce daughters that tended to have earlier first reproduction. Our findings demonstrate shared patterns as well as contrasts in age-related changes in female fertility across species of nonhuman primates and highlight species-specific behavior and life-history patterns as possible explanations for species-level differences.

Intravenous gene transfer throughout the brain of infant Old World primates using AAV

Abstract: Adeno-associated viruses (AAVs) can enable robust and safe gene delivery to the mammalian central nervous system (CNS). While the scientific community has developed numerous neurotropic AAV variants for systemic gene-transfer to the rodent brain, there are few AAVs that efficiently access the CNS of higher order primates. We describe here AAV.CAP-Mac, an engineered AAV variant that enables systemic, brain-wide gene delivery in infants of two Old World primate species—the rhesus macaque (Macaca mulatta) and the green monkey (Chlorocebus sabaeus). We identified CAP-Mac using a multi-species selection strategy, initially screening our library in the adult common marmoset (Callithrix jacchus) and narrowing our pool of test-variants for another round of selection in infant macaques. In individual characterization, CAP-Mac robustly transduces human neurons in vitro and Old World primate neurons in vivo, where it targets all lobes of cortex, the cerebellum, and multiple subcortical regions of disease relevance. We use CAP-Mac for Brainbow-like multicolor labeling of macaque neurons throughout the brain, enabling morphological reconstruction of both medium spiny neurons and cortical pyramidal cells. Because of its broad distribution throughout the brain and high neuronal efficiency in infant Old World primates compared to AAV9, CAP-Mac shows promise for researchers and clinicians alike to unlock novel, noninvasive access to the brain for efficient gene transfer.

Origins of direction selectivity in the primate retina

Abstract: Abstract From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex, but has not been found in the retina, despite significant effort. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF polyaxonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we discovered that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a door to investigation of a precortical circuitry that computes motion direction in the primate visual system.

Chimpanzee (Pan troglodytes) gaze is conspicuous at ecologically-relevant distances

Abstract: Chimpanzee (Pan troglodytes) sclera appear much darker than the white sclera of human eyes, to such a degree that the direction of chimpanzee gaze may be concealed from conspecifics. Recent debate surrounding this topic has produced mixed results, with some evidence suggesting that (1) primate gaze is indeed concealed from their conspecifics, and (2) gaze colouration is among the suite of traits that distinguish uniquely social and cooperative humans from other primates (the cooperative eye hypothesis). Using a visual modelling approach that properly accounts for specific-specific vision, we reexamined this topic to estimate the extent to which chimpanzee eye coloration is discriminable. We photographed the faces of captive chimpanzees and quantified the discriminability of their pupil, iris, sclera, and surrounding skin. We considered biases of cameras, lighting conditions, and commercial photography software along with primate visual acuity, colour sensitivity, and discrimination ability. Our visual modeling of chimpanzee eye coloration suggests that chimpanzee gaze is visible to conspecifics at a range of distances (within approximately 10 m) appropriate for many species-typical behaviours. We also found that chimpanzee gaze is discriminable to the visual system of primates that chimpanzees prey upon, Colobus monkeys. Chimpanzee sclera colour does not effectively conceal gaze, and we discuss this result with regard to the cooperative eye hypothesis, the evolution of primate eye colouration, and methodological best practices for future primate visual ecology research.

The Cortical and Subcortical Correlates of Face Pareidolia in the Macaque Brain.

Abstract: Face detection is a foundational social skill for primates. This vital function is thought to be supported by specialized neural mechanisms; however, although several face-selective regions have been identified in both humans and nonhuman primates, there is no consensus about which region(s) are involved in face detection. Here we used naturally occurring errors of face detection (i.e., objects with illusory facial features referred to as examples of "face pareidolia") to identify regions of the macaque brain implicated in face detection. Using whole-brain fMRI to test awake rhesus macaques, we discovered that a subset of face-selective patches in inferior temporal cortex (ITC), on the lower lateral edge of the superior temporal sulcus (STS), and the amygdala respond more to objects with illusory facial features than matched non-face objects. Multivariate analyses of the data revealed differences in the representation of illusory faces across the functionally defined regions of interest. These differences suggest that the cortical and subcortical face-selective regions contribute uniquely to the detection of facial features. We conclude that face detection is supported by a multiplexed system in the primate brain.

Chimpanzees organize their social relationships like humans

Abstract: Human relationships are structured in a set of layers, ordered from higher (intimate relationships) to lower (acquaintances) emotional and cognitive intensity. This structure arises from the limits of our cognitive capacity and the different amounts of resources required by different relationships. However, it is unknown whether nonhuman primate species organize their affiliative relationships following the same pattern. We here show that the time chimpanzees devote to grooming other individuals is well described by the same model used for human relationships, supporting the existence of similar social signatures for both humans and chimpanzees. Furthermore, the relationship structure depends on group size as predicted by the model, the proportion of high-intensity connections being larger for smaller groups.

Within-individual changes reveal increasing social selectivity with age in rhesus macaques

Abstract: Accumulating evidence in humans and other mammals suggests older individuals tend to have smaller social networks. Uncovering the cause of these declines is important as it can inform how changes in social relationships with age might affect health and fitness in later life. Smaller social networks might be detrimental, but may also be the result of greater selectivity in partner choice, reflecting an adaptive solution to physical or physiological limitations imposed by age. While greater selectivity with age has been shown in humans, the extent to which active ‘social selectivity’ within an individual’s lifetime occurs across the animal kingdom remains an open question. Using 8 years of longitudinal data from a population of free-ranging rhesus macaques we provide the first evidence in a non-human animal for within-individual increases in social selectivity with age. Going beyond previous cross-sectional studies, our within-individual analyses revealed that adult female macaques actively reduced the size of their networks as they aged and focused on partners previously linked to fitness benefits, including kin and partners to whom they were strongly and consistently connected earlier in life. Females spent similar amounts of time socializing as they aged, suggesting that network shrinkage does not result from lack of motivation or ability to engage. Furthermore, females remained attractive companions and were not isolated by withdrawal of social partners. Taken together, our results provide rare empirical evidence for social selectivity in non-humans, suggesting patterns of social aging in humans may be deeply rooted in primate evolution and may have adaptive value. Significance statement The narrowing of social networks and prioritization of meaningful relationships with age is commonly observed in humans. Determining whether social selectivity is exhibited by other animals remains critical to furthering our understanding of the evolution of late-life changes in sociality. Here we test key predictions from the social selectivity hypothesis and demonstrate that female rhesus macaques show within-individual changes in sociality with age that resemble the human social aging phenotype. Our use of longitudinal data to track how individuals change their social behavior within their lifetimes offers the most conclusive evidence to date that social selectivity is not a phenomenon unique to humans and therefore might have deeper evolutionary underpinnings.

Eye‐tracking as a window into primate social cognition

Abstract: Over the past decade, noninvasive, restraint‐free eye‐tracking research with primates has transformed our understanding of primate social cognition. The use of this technology with many primate species allows for the exploration and comparison of how these species attend to and understand social agents and interactions. The ability to compare and contrast the cognitive capacities of various primate species, including humans, provides insight into the evolutionary mechanisms and selective pressures that have likely shaped social cognition in similar and divergent ways across the primate order. In this review, we begin by discussing noninvasive behavioral methods used to measure primate gaze and attention before the introduction of noninvasive, restraint‐free eye‐tracking methodologies. Next, we focus on findings from recent eye‐tracking research on primate social cognition, beginning with simple visual and search mechanisms. We then discuss the results that have built on this basic understanding of how primates view images and videos, exploring discrimination and knowledge of social agents, following social cues, tracking perspectives and predicting behavior, and the combination of eye‐tracking and other behavioral and physiological methods. Finally, we discuss some future directions of noninvasive eye‐tracking research on primate social cognition and current eye‐tracking work‐in‐progress that builds on these previous studies, investigating underexplored socio‐cognitive capacities and utilizing new methodologies.

Insights Into Human and Nonhuman Primate Handedness From Measuring Both Hands

Abstract: Handedness is part of our everyday lives, but where does it come from? Researchers studying nonhuman primates and young children have approached this question from different perspectives—evolutionary and developmental, respectively. Their work converges on the conclusion that measurement matters in the science of handedness. Coming to a consensus on assessment will guide future research into the origins of handedness. A candidate behavior for promoting multidisciplinary comparison is role-differentiated bimanual manipulation.

Primate anterior insular cortex represents economic decision variables proposed by prospect theory

Abstract: In humans, risk attitude is highly context-dependent, varying with wealth levels or for different potential outcomes, such as gains or losses. These behavioral effects have been modelled using prospect theory, with the key assumption that humans represent the value of each available option asymmetrically as a gain or loss relative to a reference point. It remains unknown how these computations are implemented at the neuronal level. Here we show that macaques, like humans, change their risk attitude across wealth levels and gain/loss contexts using a token gambling task. Neurons in the anterior insular cortex (AIC) encode the 'reference point' (i.e., the current wealth level of the monkey) and reflect 'loss aversion' (i.e., option value signals are more sensitive to change in the loss than in the gain context) as postulated by prospect theory. In addition, changes in the activity of a subgroup of AIC neurons correlate with the inter-trial fluctuations in choice and risk attitude. Taken together, we show that the primate AIC in risky decision-making may be involved in monitoring contextual information used to guide the animal's willingness to accept risk.