Effects of social environments on male primate HPG and HPA axis developmental programming.

Developmental plasticity is particularly important for humans and other primates because of our extended period of growth and maturation, during which our phenotypes adaptively respond to environmental cues. The hypothalamus-pituitary-gonadal (HPG) and hypothalamus-pituitary-adrenal (HPA) axes are likely to be principal targets of developmental "programming" given their roles in coordinating fitness-relevant aspects of the phenotype, including sexual development, adult reproductive and social strategies, and internal responses to the external environment. In social animals, including humans, the social environment is believed to be an important source of cues to which these axes may adaptively respond. The effects of early social environments on the HPA axis have been widely studied in humans, and to some extent, in other primates, but there are still major gaps in knowledge specifically relating to males. There has also been relatively little research examining the role that social environments play in developmental programming of the HPG axis or the HPA/HPG interface, and what does exist disproportionately focuses on females. These topics are likely understudied in males in part due to the difficulty of identifying developmental milestones in males relative to females and the general quiescence of the HPG axis prior to maturation. However, there are clear indicators that early life social environments matter for both sexes. In this review, we examine what is known about the impact of social environments on HPG and HPA axis programming during male development in humans and nonhuman primates, including the role that epigenetic mechanisms may play in this programming. We conclude by highlighting important next steps in this research area.

Behavioral thermoregulation in primates: A review of literature and future avenues.

Primates face severe challenges from climate change, with warming expected to increase animals' thermoregulatory demands. Primates have limited long-term options to cope with climate change, but possess a remarkable capacity for behavioral plasticity. This creates an urgency to better understand the behavioral mechanisms primates use to thermoregulate. While considerable information exists on primate behavioral thermoregulation, it is often scattered in the literature in a manner that is difficult to integrate. This review evaluates the status of the available literature on primate behavioral thermoregulation to facilitate future research. We surveyed peer-reviewed publications on primate thermoregulation for N = 17 behaviors across four thermoregulatory categories: activity budgeting, microhabitat use, body positioning, and evaporative cooling. We recorded data on the primate taxa evaluated, support for a thermoregulatory function, thermal variable assessed, and naturalistic/manipulative study conditions. Behavioral thermoregulation was pervasive across primates, with N = 721 cases of thermoregulatory behaviors identified across N = 284 published studies. Most genera were known to utilize multiple behaviors ( x ¯ = 4.5 ± 3.1 behaviors/genera). Activity budgeting behaviors were the most commonly encountered category in the literature (54.5% of cases), while evaporative cooling behaviors were the least represented (6.9% of cases). Behavioral thermoregulation studies were underrepresented for certain taxonomic groups, including lemurs, lorises, galagos, and Central/South American primates, and there were large within-taxa disparities in representation of genera. Support for a thermoregulatory function was consistently high across all behaviors, spanning both hot- and cold-avoidance strategies. This review reveals asymmetries in the current literature and avenues for future research. Increased knowledge of the impact thermoregulatory behaviors have on biologically relevant outcomes is needed to better assess primate responses to warming environments and develop early indicators of thermal stress.

The growth factor EPIREGULIN promotes basal progenitor cell proliferation in the developing neocortex.

Neocortex expansion during evolution is linked to higher numbers of neurons, which are thought to result from increased proliferative capacity and neurogenic potential of basal progenitor cells during development. Here, we show that EREG, encoding the growth factor EPIREGULIN, is expressed in the human developing neocortex and in gorilla cerebral organoids, but not in the mouse neocortex. Addition of EPIREGULIN to the mouse neocortex increases proliferation of basal progenitor cells, whereas EREG ablation in human cortical organoids reduces proliferation in the subventricular zone. Treatment of cortical organoids with EPIREGULIN promotes a further increase in proliferation of gorilla but not of human basal progenitor cells. EPIREGULIN competes with the epidermal growth factor (EGF) to promote proliferation, and inhibition of the EGF receptor abrogates the EPIREGULIN-mediated increase in basal progenitor cells. Finally, we identify putative cis-regulatory elements that may contribute to the observed inter-species differences in EREG expression. Our findings suggest that species-specific regulation of EPIREGULIN expression may contribute to the increased neocortex size of primates by providing a tunable pro-proliferative signal to basal progenitor cells in the subventricular zone.

An optrode array for spatiotemporally-precise large-scale optogenetic stimulation of deep cortical layers in non-human primates.

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.

Pathways for Naturalistic Looking Behavior in Primate II. Superior Colliculus Integrates Parallel Top-down and Bottom-up Inputs.

Volitional signals for gaze control are provided by multiple parallel pathways converging on the midbrain superior colliculus (SC), whose deeper layers output to the brainstem gaze circuits. In the first of two papers (Takahashi and Veale, 2023), we described the properties of gaze behavior of several species under both laboratory and natural conditions, as well as the current understanding of the brainstem and spinal cord circuits implementing gaze control in primate. In this paper, we review the parallel pathways by which sensory and task information reaches SC and how these sensory and task signals interact within SC's multilayered structure. This includes both bottom-up (world statistics) signals mediated by sensory cortex, association cortex, and subcortical structures, as well as top-down (goal and task) influences which arrive via either direct excitatory pathways from cerebral cortex, or via indirect basal ganglia relays resulting in inhibition or dis-inhibition as appropriate for alternative behaviors. Models of attention such as saliency maps serve as convenient frameworks to organize our understanding of both the separate computations of each neural pathway, as well as the interaction between the multiple parallel pathways influencing gaze. While the spatial interactions between gaze's neural pathways are relatively well understood, the temporal interactions between and within pathways will be an important area of future study, requiring both improved technical methods for measurement and improvement of our understanding of how temporal dynamics results in the observed spatiotemporal allocation of gaze.

The prefrontal cortex: from monkey to man.

The prefrontal cortex is so important to human beings that, if deprived of it, our behaviour is reduced to action-reactions and automatisms, with no ability to make deliberate decisions. Why does the prefrontal cortex hold such importance in humans? In answer, this review draws on the proximity between humans and other primates, which enables us, through comparative anatomical-functional analysis, to understand the cognitive functions we have in common and specify those that distinguish humans from their closest cousins. First, a focus on the lateral region of the prefrontal cortex illustrates the existence of a continuum between rhesus monkeys (the most studied primates in neuroscience) and humans for most of the major cognitive functions in which this region of the brain plays a central role. This continuum involves the presence of elementary mental operations in the rhesus monkey (e.g. working memory or response inhibition) that are constitutive of 'macro-functions' such as planning, problem-solving and even language production. Second, the human prefrontal cortex has developed dramatically compared to that of other primates. This increase seems to concern the most anterior part (the frontopolar cortex). In humans, the development of the most anterior prefrontal cortex is associated with three major and interrelated cognitive changes: (i) a greater working memory capacity, allowing for greater integration of past experiences and prospective futures; (ii) a greater capacity to link discontinuous or distant data, whether temporal or semantic; and (iii) a greater capacity for abstraction, allowing humans to classify knowledge in different ways, to engage in analogical reasoning or to acquire abstract values that give rise to our beliefs and morals. Together, these new skills enable us, among other things, to develop highly sophisticated social interactions based on language, enabling us to conceive beliefs and moral judgements and to conceptualize, create and extend our vision of our environment beyond what we can physically grasp. Finally, a model of the transition of prefrontal functions between humans and non-human primates concludes this review.

Anatomy of the auditory cortex then and now.

Using neuroanatomical investigations in the macaque, Deepak Pandya and his colleagues have established the framework for auditory cortex organization, with subdivisions into core and belt areas. This has aided subsequent neurophysiological and imaging studies in monkeys and humans, and a nomenclature building on Pandya's work has also been adopted by the Human Connectome Project. The foundational work by Pandya and his colleagues is highlighted here in the context of subsequent and ongoing studies on the functional anatomy and physiology of auditory cortex in primates, including humans, and their relevance for understanding cognitive aspects of speech and language.

Energetic costs of feeding in 12 species of small-bodied primates.

There are no comparative, empirical studies of the energetic costs of feeding in mammals. As a result, we lack physiological data to better understand the selection pressures on the mammalian feeding apparatus and the influence of variables such as food geometric and material properties. This study investigates interspecific scaling of the net energetic costs of feeding in relation to body size, jaw-adductor muscle mass and food properties in a sample of 12 non-human primate species ranging in size from 0.08 to 4.2 kg. Net energetic costs during feeding were measured by indirect calorimetry for a variety of pre-cut and whole raw foods varying in geometric and material properties. Net feeding costs were determined in two ways: by subtracting either the initial metabolic rate prior to feeding or subtracting the postprandial metabolic rate. Interspecific scaling relationships were evaluated using pGLS and OLS regression. Net feeding costs scale negatively relative to both body mass and jaw-adductor mass. Large animals incur relatively lower feeding costs indicating that small and large animals experience and solve mechanical challenges in relation to energetics in different ways. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.

Towards an integrated understanding of dietary phenotypes.

Diet and nutrition comprise a complex, multi-faceted interface between animal biology and food environments. With accumulating information on the many facets of this association arises a need for systems-based approaches that integrate dietary components and their links with ecology, feeding, post-ingestive processes and the functional and ecological consequences of these interactions. We briefly show how a modelling approach, nutritional geometry, has used the experimental control afforded in laboratory studies to begin to unravel these links. Laboratory studies, however, have limited ability to establish whether and how the feeding and physiological mechanisms interface with realistic ecological environments. We next provide an overview of observational field studies of free-ranging primates that have examined this, producing largely correlative data suggesting that similar feeding mechanisms operate in the wild as in the laboratory. Significant challenges remain, however, in establishing causal links between feeding, resource variation and physiological processes in the wild. We end with a more detailed account of two studies of temperate primates that have capitalized on the discrete variation provided by seasonal environments to strengthen causal inference in field studies and link patterns of intake to dynamics of nutrient processing. This article is part of the theme issue 'Food processing and nutritional assimilation in animals'.

The basal ganglia are a target for sensorimotor domains in posterior parietal, premotor, and motor cortex in primates.

Our research focused on defining and characterizing parieto-frontal circuits for specific actions in primates. Part of the posterior parietal cortex is divided into eight or more domains where electrical stimulation evokes a meaningful complex movement. Domains in the posterior parietal cortex compete with each other over excitatory connections that activate inhibitory neurons, while selectively activating functionally matched domains in the premotor cortex and motor cortex. Thus, the selection process involves competition and cooperation between domains over three different regions of cortex. In addition, projections from functionally matched domains in motor regions converge in the matrix of the striatum, whereas projections from different functionally unmatched domains are separate. Thus, the projections of action-specific domains include the basal ganglia, where actions can be permitted or blocked.

Specialized Networks for Social Cognition in the Primate Brain.

Primates have evolved diverse cognitive capabilities to navigate their complex social world. To understand how the brain implements critical social cognitive abilities, we describe functional specialization in the domains of face processing, social interaction understanding, and mental state attribution. Systems for face processing are specialized from the level of single cells to populations of neurons within brain regions to hierarchically organized networks that extract and represent abstract social information. Such functional specialization is not confined to the sensorimotor periphery but appears to be a pervasive theme of primate brain organization all the way to the apex regions of cortical hierarchies. Circuits processing social information are juxtaposed with parallel systems involved in processing nonsocial information, suggesting common computations applied to different domains. The emerging picture of the neural basis of social cognition is a set of distinct but interacting subnetworks involved in component processes such as face perception and social reasoning, traversing large parts of the primate brain.

Transcranial magnetic stimulation in non-human primates: A systematic review.

Transcranial magnetic stimulation (TMS) is widely employed as a tool to investigate and treat brain diseases. However, little is known about the direct effects of TMS on the brain. Non-human primates (NHPs) are a valuable translational model to investigate how TMS affects brain circuits given their neurophysiological similarity with humans and their capacity to perform complex tasks that approach human behavior. This systematic review aimed to identify studies using TMS in NHPs as well as to assess their methodological quality through a modified reference checklist. The results show high heterogeneity and superficiality in the studies regarding the report of the TMS parameters, which have not improved over the years. This checklist can be used for future TMS studies with NHPs to ensure transparency and critical appraisal. The use of the checklist would improve methodological soundness and interpretation of the studies, facilitating the translation of the findings to humans. The review also discusses how advancements in the field can elucidate the effects of TMS in the brain.

The impact of sanctuary visits on children's knowledge and attitudes toward primate welfare and conservation.

Primate sanctuaries provide a solution for the increasing number of primates being taken from their home countries to support the demands of the illegal pet trade. To help end the primate trade and raise awareness about the risks this trade poses to delicate ecosystems, sanctuaries are increasingly developing conservation education programs. Education and raising awareness must be one of the primary roles of primate sanctuaries. However, there are few evaluations of the impacts of conservation education programs for school children published in scientific literature. To address this gap, we conducted an evaluation of educator-led visits of school children at Fundació Mona, a primate sanctuary located in Catalunya, Spain. Questionnaires for an experimental and control group were conducted with 3,205 school children, ages 8 to 18 from 83 different schools, to evaluate changes in their attitudes and knowledge of primate welfare and conservation. We found that Fundació Mona's program of environmental activities had a positive impact on children, both female and male students, in terms of attitudes and knowledge of primate welfare and conservation. Although female students gave better responses regarding welfare and conservation, all children showed gains in pro-conservation responses. This study demonstrates that environmental education activities focused on children can help shape a change in knowledge and attitudes toward primate welfare and conservation. Educator-led visits of school children to primate sanctuaries such as Fundació Mona can also serve to amplify biodiversity conservation messages among children and their families. We encourage primate sanctuaries to promote empirical studies of attitudes and knowledge of primate welfare and conservation and to conduct systematical evaluations to strengthen their educational activities.

Genetic Approaches for Neural Circuits Dissection in Non-human Primates.

Genetic tools, which can be used for the morphology study of specific neurons, pathway-selective connectome mapping, neuronal activity monitoring, and manipulation with a spatiotemporal resolution, have been widely applied to the understanding of complex neural circuit formation, interactions, and functions in rodents. Recently, similar genetic approaches have been tried in non-human primates (NHPs) in neuroscience studies for dissecting the neural circuits involved in sophisticated behaviors and clinical brain disorders, although they are still very preliminary. In this review, we introduce the progress made in the development and application of genetic tools for brain studies on NHPs. We also discuss the advantages and limitations of each approach and provide a perspective for using genetic tools to study the neural circuits of NHPs.

The dorsal stream of visual processing and action-specific domains in parietal and frontal cortex in primates.

This review summarizes our findings obtained from over 15 years of research on parietal-frontal networks involved in the dorsal stream of cortical processing. We have presented considerable evidence for the existence of similar, partially independent, parietal-frontal networks involved in specific motor actions in a number of primates. These networks are formed by connections between action-specific domains representing the same complex movement evoked by electrical microstimulation. Functionally matched domains in the posterior parietal (PPC) and frontal (M1-PMC) motor regions are hierarchically related. M1 seems to be a critical link in these networks, since the outputs of M1 are essential to the evoked behavior, whereas PPC and PMC mediate complex movements mostly via their connections with M1. Thus, lesioning or deactivating M1 domains selectively blocks matching PMC and PPC domains, while having limited impact on other domains. When pairs of domains are stimulated together, domains within the same parietal-frontal network (matching domains) are cooperative in evoking movements, while they are mainly competitive with other domains (mismatched domains) within the same set of cortical areas. We propose that the interaction of different functional domains in each cortical region (as well as in striatum) occurs mainly via mutual suppression. Thus, the domains at each level are in competition with each other for mediating one of several possible behavioral outcomes.

The fire of evolution: energy expenditure and ecology in primates and other endotherms.

Total energy expenditure (TEE) represents the total energy allocated to growth, reproduction and body maintenance, as well as the energy expended on physical activity. Early experimental work in animal energetics focused on the costs of specific tasks (basal metabolic rate, locomotion, reproduction), while determination of TEE was limited to estimates from activity budgets or measurements of subjects confined to metabolic chambers. Advances in recent decades have enabled measures of TEE in free-living animals, challenging traditional additive approaches to understanding animal energy budgets. Variation in lifestyle and activity level can impact individuals' TEE on short time scales, but interspecific differences in TEE are largely shaped by evolution. Here, we review work on energy expenditure across the animal kingdom, with a particular focus on endotherms, and examine recent advances in primate energetics. Relative to other placental mammals, primates have low TEE, which may drive their slow pace of life and be an evolved response to the challenges presented by their ecologies and environments. TEE variation among hominoid primates appears to reflect adaptive shifts in energy throughput and allocation in response to ecological pressures. As the taxonomic breadth and depth of TEE data expand, we will be able to test additional hypotheses about how energy budgets are shaped by environmental pressures and explore the more proximal mechanisms that drive intra-specific variation in energy expenditure.

Pump the brakes! The hindlimbs of three-toed sloths decelerate and support suspensory locomotion.

Modern tree sloths are one of few mammalian taxa for which quadrupedal suspension is obligatory. Sloth limb musculature is specialized for slow velocity, large force contractions that stabilize their body below branches and conserve energy during locomotion. However, it is unknown whether two- and three-toed sloths converge in their use of limb kinetics and if these patterns are comparable to how primates perform arboreal suspensory locomotion. This study addressed this need by collecting limb loading data in three-toed sloths (Bradypus variegatus; N=5) during suspensory walking. Sloths performed locomotor trials at their preferred speed on an instrumented beam apparatus with a force platform as the central supporting segment. Peak forces and impulses of the forelimb and hindlimb were recorded and analyzed in three dimensions. The hindlimbs of B. variegatus apply large braking forces greater in magnitude than peak forces generated by the forelimbs in propulsion, a pattern consistent with that observed in two-toed sloths. However, B. variegatus exhibits hindlimb-biased body weight support in vertical peak forces and impulse, with appreciable laterally directed forces in each limb pair, both of which vary from limb loading distributions in two-toed sloths. Moreover, body weight distribution between limb pairs is opposite to that employed by primates during quadrupedal suspension. Thus, there appear to be multiple strategies for achieving suspensory locomotion in arboreal mammals. These differences may be attributable to anatomical variation or phylogenetic position, but as of yet an explanation remains unknown. Future EMG analyses are expected to provide insight into how specific hindlimb muscle groups contribute to braking forces and stabilizing the center of mass of sloths during suspension.

Perception of color in primates: A conceptual color neurons hypothesis.

Perception of color by humans and other primates is a complex problem, studied by neurophysiology, psychophysiology, psycholinguistics, and even philosophy. Being mostly trichromats, simian primates have three types of opsin proteins, expressed in cone neurons in the eye, which allow for the sensing of color as the physical wavelength of light. Further, in neural networks of the retina, the coding principle changes from three types of sensor proteins to two opponent channels: activity of one type of neuron encode the evolutionarily ancient blue-yellow axis of color stimuli, and another more recent evolutionary channel, encoding the axis of red-green color stimuli. Both color channels are distinctive in neural organization at all levels from the eye to the neocortex, where it is thought that the perception of color (as philosophical qualia) emerges from the activity of some neuron ensembles. Here, using data from neurophysiology as a starting point, we propose a hypothesis on how the perception of color can be encoded in the activity of certain neurons in the neocortex. These conceptual neurons, herein referred to as 'color neurons', code only the hue of the color of visual stimulus, similar to place cells and number neurons, already described in primate brains. A case study with preliminary, but direct, evidence for existing conceptual color neurons in the human brain was published in 2008. We predict that the upcoming studies in non-human primates will be more extensive and provide a more detailed description of conceptual color neurons.

Allocentric information represented by self-referenced spatial coding in the primate medial temporal lobe.

For living organisms, the ability to acquire information regarding the external space around them is critical for future actions. While the information must be stored in an allocentric frame to facilitate its use in various spatial contexts, each case of use requires the information to be represented in a particular self-referenced frame. Previous studies have explored neural substrates responsible for the linkage between self-referenced and allocentric spatial representations based on findings in rodents. However, the behaviors of rodents are different from those of primates in several aspects; for example, rodents mainly explore their environments through locomotion, while primates use eye movements. In this review, we discuss the brain mechanisms responsible for the linkage in nonhuman primates. Based on recent physiological studies, we propose that two types of neural substrates link the first-person perspective with allocentric coding. The first is the view-center background signal, which represents an image of the background surrounding the current position of fixation on the retina. This perceptual signal is transmitted from the ventral visual pathway to the hippocampus (HPC) via the perirhinal cortex and parahippocampal cortex. Because images that share the same objective-position in the environment tend to appear similar when seen from different self-positions, the view-center background signals are easily associated with one another in the formation of allocentric position coding and storage. The second type of neural substrate is the HPC neurons' dynamic activity that translates the stored location memory to the first-person perspective depending on the current spatial context.

Cytology, architecture, development, and connections of the primate striatum: Hints for human pathology.

Degeneration of neurons and circuits across the striatum shows stereotyped time-course and spatial topography patterns that are distinct for Huntington's disease, Parkinson's disease, or the Tauopathies. These patterns of neurodegeneration in humans have not yet been systematically related to developmental, connectional, cellular, and chemical factors studied in human and non-human primates, that may underlie potential differences in selective vulnerability across striatal sectors. Relating primate anatomy to human pathology could provide new venues for identifying molecular, cellular, and connectional factors linked to the degeneration of striatal neurons and circuits. This review describes and summarizes several developmental, cellular, structural, and connectional features of the primate striatum in relation to patterns of neurodegeneration in the striatum of humans and of non-human primate models. We review (1) the types of neurons in the primate striatum, (2) the cyto-, myelo-, and chemoarchitecture of the primate striatum, (3) the developmental origin of the striatum in light of modern patterning studies, (4) the organization of corticostriatal projections in relation to cortical types, and (5) the topography and time-course of neuron loss, glial reaction, and protein aggregation induced by neurodegenerative diseases in humans and in non-human primate models across striatal sectors and their corresponding cortical areas. We summarize current knowledge about key aspects of primate striatal anatomy and human pathology and indicate knowledge gaps that should be addressed in future studies. We aim to identify factors for selective vulnerability to neurodegeneration of striatal neurons and circuits and obtain hints that could help elucidate striatal pathology in humans.