Behavior In Nonhuman Primates Research Articles

Supporting generalization in non-human primate behavior by tapping into structural knowledge: Examples from sensorimotor mappings, inference, and decision-making.

The complex behaviors we ultimately wish to understand are far from those currently used in systems neuroscience laboratories. A salient difference are the closed loops between action and perception prominently present in natural but not laboratory behaviors. The framework of reinforcement learning and control naturally wades across action and perception, and thus is poised to inform the neurosciences of tomorrow, not only from a data analyses and modeling framework, but also in guiding experimental design. We argue that this theoretical framework emphasizes active sensing, dynamical planning, and the leveraging of structural regularities as key operations for intelligent behavior within uncertain, time-varying environments. Similarly, we argue that we may study natural task strategies and their neural circuits without over-training animals when the tasks we use tap into our animal's structural knowledge. As proof-of-principle, we teach animals to navigate through a virtual environment - i.e., explore a well-defined and repetitive structure governed by the laws of physics - using a joystick. Once these animals have learned to 'drive', without further training they naturally (i) show zero- or one-shot learning of novel sensorimotor contingencies, (ii) infer the evolving path of dynamically changing latent variables, and (iii) make decisions consistent with maximizing reward rate. Such task designs allow for the study of flexible and generalizable, yet controlled, behaviors. In turn, they allow for the exploitation of pillars of intelligence - flexibility, prediction, and generalization -, properties whose neural underpinning have remained elusive.

Acquisition of object-robbing and object/food-bartering behaviours: a culturally maintained token economy in free-ranging long-tailed macaques

The token exchange paradigm shows that monkeys and great apes are able to use objects as symbolic tools to request specific food rewards. Such studies provide insights into the cognitive underpinnings of economic behaviour in non-human primates. However, the ecological validity of these laboratory-based experimental situations tends to be limited. Our field research aims to address the need for a more ecologically valid primate model of trading systems in humans. Around the Uluwatu Temple in Bali, Indonesia, a large free-ranging population of long-tailed macaques spontaneously and routinely engage in token-mediated bartering interactions with humans. These interactions occur in two phases: after stealing inedible and more or less valuable objects from humans, the macaques appear to use them as tokens, by returning them to humans in exchange for food. Our field observational and experimental data showed (i) age differences in robbing/bartering success, indicative of experiential learning, and (ii) clear behavioural associations between value-based token possession and quantity or quality of food rewards rejected and accepted by subadult and adult monkeys, suggestive of robbing/bartering payoff maximization and economic decision-making. This population-specific, prevalent, cross-generational, learned and socially influenced practice may be the first example of a culturally maintained token economy in free-ranging animals.This article is part of the theme issue ‘Existence and prevalence of economic behaviours among non-human primates'.

Death Avoidance Behavior of Accidentally Injured Cub in Platyrrhini: An Opportunistic Observation Record

Introduction: Infraorder Platyrrhini is composed of species with complex social structures, but information about their interaction with death is scarce in the literature, as already registered for old world monkeys. This work concern of death avoidance behavior recorded in a group of Callithrix penicillata (E. Geoffroy, 1812) (Primates, Callitrichidae). Material and Methods: This is a study made it through opportunistic observation of an interaction between a mother and her cub, accidentally injured and on the deathbed. The detailed description of the phenomenon occurred through all occurrence sampling, and was counted on the testimony of local residents. For better data exposure, an etogram was constructed, containing all the observed behaviors, in sequence, from the beginning to the end of the sampling. Results: In all, 10 individuals participated in the observations, and 16 behavioral acts were observed during 6 days of observation of the interaction mother-child injured-other individuals. The behaviors indicated a high degree of stress on the part of all involved, as well as the mother's attempt to withdraw her cub from the area in which was. The mother also tried to bring it to your back. There were other individuals in the group, possibly to assist in caring for the cub. 1 Conclusion: This work is unpublished for the specie in question and reaffirms its social character. The observations open spaces for further investigation into similar behaviors in human and non-human primates as well as the phylogenetic relationship between them.

PSV-7 Effects of music stimulus on behavior response, cortisol level and immunity horizontal of growing pigs

Abstract Enrichment environment is widely used to improve the welfare of domestic animals and satisfy their natural behavior. Music as an enriched environment can reduce abnormal behavior in humans, non-human primates and rodents. The aim of this study was to investigate the effects of repeated music stimuli on the behavior, physiology and immunity of growing pigs. A total of 72 5-week-old hybrid piglets (Large White × Duroc × Minpig) were randomly divided into three treatments groups of the music group (Mozart K.448, 65–70 dB), the noise group (mechanical noise, 85–90 dB) and the control group (silence, less than 40dB). During 60 days of auditory exposure, the behavioral responses, cortisol level and immune horizontal of the piglets were measured. The results showed that the active behavior of the growing pigs increased and lying behavior decreased in the music group compared to the control group (P < 0.05). The music stimulus increased tail wagging, tail in curl and playing behaviors (P < 0.05). The noise stimulus increased aggressive behavior (P < 0.05) but had no effect on the exploring and manipulative behaviors (P > 0.05). The frequency of the event behaviors decreased with the time of auditory stimuli (P < 0.05). Short-term music stimulus had a lower cortisol level than the noise and control groups (P < 0.05). Long-term music stimulus increased the level of IgG, IL-2 and IFN-γ (P < 0.05) and decreased the IL-4 level (P < 0.05). Noise stimulus reduced the level of IgG (P < 0.05) but had no effect on the level of IL-2, IL-4 and IFN-γ (P > 0.05). In conclusion, music stimulus triggers the pigs to show more positive behaviors, and the short-term music stimulus can reduce the stress response, while the long-term music stimulus can enhance the immune responses in the growing pigs.

How to Get the Biggest Slice of the Cake. A Comparative View of Social Behaviour and Resource Access in Human Children and Nonhuman Primates.

Social complexity results from engaging in different classes of social behaviour. The presence of different classes of social behaviour is reflected in multidimensional concepts of social asymmetry, found in both human and nonhuman primates. Based on an overview of such concepts, we propose that three classes of social behaviour are involved in having access to scarce and desired resources: next to aggressive and affiliative behaviour, also action indicating behaviour (i.e., inspire another individual to follow one’s example or intentions) may lead to resource access. Studies with nonhuman primate and human children show that the contribution of aggression and affiliation to resource access has been widely documented and that there is initial support for action indicating behaviour. In addition, the studies show similarities and differences in conceptualization and approach that may inspire future research. Future research should address the (in)dependency of the behavioural dimensions, their relative importance, individual differences in combined expression and the type of resources accessed. Only a multi-dimensional view on behaviour leading to resource access will highlight the benefits of social complexity.

Flexible Working Memory Through Selective Gating and Attentional Tagging.

Working memory is essential: it serves to guide intelligent behavior of humans and nonhuman primates when task-relevant stimuli are no longer present to the senses. Moreover, complex tasks often require that multiple working memory representations can be flexibly and independently maintained, prioritized, and updated according to changing task demands. Thus far, neural network models of working memory have been unable to offer an integrative account of how such control mechanisms can be acquired in a biologically plausible manner. Here, we present WorkMATe, a neural network architecture that models cognitive control over working memory content and learns the appropriate control operations needed to solve complex working memory tasks. Key components of the model include a gated memory circuit that is controlled by internal actions, encoding sensory information through untrained connections, and a neural circuit that matches sensory inputs to memory content. The network is trained by means of a biologically plausible reinforcement learning rule that relies on attentional feedback and reward prediction errors to guide synaptic updates. We demonstrate that the model successfully acquires policies to solve classical working memory tasks, such as delayed recognition and delayed pro-saccade/anti-saccade tasks. In addition, the model solves much more complex tasks, including the hierarchical 12-AX task or the ABAB ordered recognition task, both of which demand an agent to independently store and updated multiple items separately in memory. Furthermore, the control strategies that the model acquires for these tasks subsequently generalize to new task contexts with novel stimuli, thus bringing symbolic production rule qualities to a neural network architecture. As such, WorkMATe provides a new solution for the neural implementation of flexible memory control.

Azure-winged magpies\u2019 decisions to share food are contingent on the presence or absence of food for the recipient

Helping others is a key feature of human behavior. However, recent studies render this feature not uniquely human, and describe discoveries of prosocial behavior in non-human primates, other social mammals, and most recently in some bird species. Nevertheless, the cognitive underpinnings of this prosociality; i.e., whether animals take others’ need for help into account, often remain obscured. In this study, we take a first step in investigating prosociality in azure-winged magpies by presenting them with the opportunity to share highly desired food with their conspecifics i) in a situation in which these conspecifics had no such food, ii) in a situation in which they too had access to that highly desired food, and iii) in an open, base-line, situation where all had equal access to the same food and could move around freely. We find that azure-winged magpies regularly share high-value food items, preferably with, but not restricted to, members of the opposite sex. Most notably, we find that these birds, and specifically the females, seem to differentiate between whether others have food or do not have food, and subsequently cater to that lack. Begging calls by those without food seem to function as cues that elicit the food-sharing, but the response to that begging is condition-dependent. Moreover, analyses on a restricted dataset that excluded those events in which there was begging showed exactly the same patterns, raising the possibility that the azure-winged magpies might truly notice when others have access to fewer resources (even in the absence of vocal cues). This sharing behavior could indicate a high level of social awareness and prosociality that should be further investigated. Further studies are needed to establish the order of intentionality at play in this system, and whether azure-winged magpies might be able to attribute desire states to their conspecifics.

Early childhood general anesthesia exposure associated with later developmental delay: A national population-based cohort study.

Exposure to general anesthesia has been reported to induce neurotoxicity, impair learning, memory, attention, motor functions, as well as affect behavior in adult rodents and nonhuman primates. Though many have speculated similar effects in humans, previous literature has shown conflicting findings. To investigate the differences in risk of developmental delay among young children exposed to general anesthesia compared to matched unexposed individuals, a population-based cohort study was conducted with a longitudinal dataset spanning 2000 to 2013 from the Taiwan National Health Insurance Research Database (NHIRD). Procedure codes were used to identify children who received anesthesia. For each exposed child, two unexposed children matched by gender and age were enrolled into the comparison cohort. Neurocognitive outcome was measured by the presence of ICD-9-CM codes related to developmental delay (DD). Cox regression models were used to obtain hazard ratios of developing DD after varying levels of anesthesia exposure. After excluding 4,802 individuals who met the exclusion criteria, a total of 11,457 children who received general anesthesia before two years of age was compared to 22,914 children (matched by gender and age) unexposed to anesthesia. Increased risk of DD was observed in the exposure group with a hazard ratio (HR) of 1.320 (95% CI 1.143–1.522, P < 0.001). Subgroup analysis demonstrated further elevated risks of DD with multiple anesthesia exposures (1 anesthesia event: HR 1.145, 95% CI 1.010–1.246, P = 0.04; 2 anesthesia events: HR 1.476, 95% CI 1.155–1.887, P = 0.005; ≥3 anesthesia events: HR 2.222, 95% CI 1.810–2.621, P < 0.001) and longer total anesthesia durations (Total anesthesia <2 hours: HR 1.124, 95% CI 1.003–1.499, P = 0.047; Total anesthesia 2–4 hours: HR 1.450, 95% CI 1.157–1.800, P = 0.004; Total anesthesia > 4 hours: HR 1.598, 95% CI 1.343–1.982, P < 0.001) compared with children unexposed to anesthesia. These results suggest that children exposed to general anesthesia before two years of age have an increased risk of DD. This risk is further elevated with increased frequency of anesthesia, and longer total anesthesia duration. The findings of this study should prompt clinical practitioners to proceed with caution when assessing young patients and planning managements involving procedures requiring general anesthesia.

Just kidding: the evolutionary roots of playful teasing.

Accounts of teasing have a long history in psychological and sociological research, yet teasing itself is vastly underdeveloped as a topic of study. As a phenomenon that moves along the border between aggression and play, teasing presents an opportunity to investigate key foundations of social and mental life. Developmental studies suggest that preverbal human infants already playfully tease their parents by performing ‘the unexpected,’ apparently deliberately violating the recipient's expectations to create a shared humorous experience. Teasing behaviour may be phylogenetically old and perhaps an evolutionary precursor to joking. In this review, we present preliminary evidence suggesting that non-human primates also exhibit playful teasing. In particular, we argue that great apes display three types of playful teasing described in preverbal human infants: teasing with offer and withdrawal, provocative non-compliance and disrupting others' activities. We highlight the potential of this behaviour to provide a window into complex socio-cognitive processes such as attribution of others’ expectations and, finally, we propose directions for future research and call for systematic studies of teasing behaviour in non-human primates.

Neuronavigated Repetitive Transcranial Ultrasound Stimulation Induces Long-Lasting and Reversible Effects on Oculomotor Performance in Non-human Primates.

Since the late 2010s, Transcranial Ultrasound Stimulation (TUS) has been used experimentally to carryout safe, non-invasive stimulation of the brain with better spatial resolution than Transcranial Magnetic Stimulation (TMS). This innovative stimulation method has emerged as a novel and valuable device for studying brain function in humans and animals. In particular, single pulses of TUS directed to oculomotor regions have been shown to modulate visuomotor behavior of non-human primates during 100 ms ultrasound pulses. In the present study, a sustained effect was induced by applying 20-s trains of neuronavigated repetitive Transcranial Ultrasound Stimulation (rTUS) to oculomotor regions of the frontal cortex in three non-human primates performing an antisaccade task. With the help of MRI imaging and a frame-less stereotactic neuronavigation system (SNS), we were able to demonstrate that neuronavigated TUS (outside of the MRI scanner) is an efficient tool to carry out neuromodulation procedures in non-human primates. We found that, following neuronavigated rTUS, saccades were significantly modified, resulting in shorter latencies compared to no-rTUS trials. This behavioral modulation was maintained for up to 20 min. Oculomotor behavior returned to baseline after 18–31 min and could not be significantly distinguished from the no-rTUS condition. This study is the first to show that neuronavigated rTUS can have a persistent effect on monkey behavior with a quantified return-time to baseline. The specificity of the effects could not be explained by auditory confounds.

On the evolution of baboon greeting rituals.

To balance the trade-offs of male co-residence, males living in multi-male groups may exchange ritualized greetings. Although these non-aggressive signals are widespread in the animal kingdom, the repertoire described in the genus Papio is exceptional, involving potentially harmful behaviours such as genital fondling. Such greetings are among the most striking male baboon social interactions, yet their function remains disputed. Drawing on the comprehensive analysis from our own research on wild Guinea baboons, combined with a survey of the literature into other baboon species, we review the form and function of male-male ritualized greetings and their relation to the various social systems present in this genus. These ritualized signals differ between species in their occurrence, form and function. While ritualized greetings are rare in species with the most intense contest competition, the complexity of and risk involved in greeting rituals increase with the degree of male-male tolerance and cooperation. The variety of societies found in this genus, combined with its role as a model for human socioecological evolution, sheds light on the evolution of ritualized behaviour in non-human primates and rituals in humans. This article is part of the theme issue 'Ritual renaissance: new insights into the most human of behaviours'.

Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex

Optogenetics has become an indispensable tool for investigating brain functions. Although non-human primates are particularly useful models for understanding the functions and dysfunctions of the human brain, application of optogenetics to non-human primates is still limited. In the present study, we generate an effective adeno-associated viral vector serotype DJ to express channelrhodopsin-2 (ChR2) under the control of a strong ubiquitous CAG promoter and inject into the somatotopically identified forelimb region of the primary motor cortex in macaque monkeys. ChR2 is strongly expressed around the injection sites, and optogenetic intracortical microstimulation (oICMS) through a homemade optrode induces prominent cortical activity: Even single-pulse, short-duration oICMS evokes long-lasting repetitive firings of cortical neurons. In addition, oICMS elicits distinct forelimb movements and muscle activity, which are comparable to those elicited by conventional electrical ICMS. The present study removes obstacles to optogenetic manipulation of neuronal activity and behaviors in non-human primates.

Targeted Transgene Expression in Cholinergic Interneurons in the Monkey Striatum Using Canine Adenovirus Serotype 2 Vectors.

The striatum, the main input structure of the basal ganglia, is critical for action selection and adaptive motor control. To understand the neuronal mechanisms underlying these functions, an analysis of microcircuits that compose the striatum is necessary. Among these, cholinergic interneurons (ChIs) provide intrinsic striatal innervation whose dysfunction is implicated in neuropsychiatric diseases, such as Parkinson’s disease and Tourette syndrome. The ability to experimentally manipulate the activity of ChIs is critical to gain insights into their contribution to the normal function of the striatum and the emergence of behavioral abnormalities in pathological states. In this study, we generated and tested CAV-pChAT-GFP, a replication-defective canine adenovirus type 2 (CAV-2) vector carrying the green fluorescent protein (GFP) sequence under the control of the human choline acetyltransferase (ChAT) promoter. We first tested the potential specificity of CAV-pChAT-GFP to label striatal ChIs in a rat before performing experiments on two macaque monkeys. In the vector-injected rat and monkey striatum, we found that GFP expression preferentially colocalized with ChAT-immunoreactivity throughout the striatum, including those from local circuit interneurons. CAV-2 vectors containing transgene driven by the ChAT promoter provide a powerful tool for investigating ChI contributions to circuit function and behavior in nonhuman primates.

R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI)‐induced Vocalizations and Observable Behavior in Nonhuman Primates

Many psychiatric disorders include elements of dysfunctional social behavior. Understanding the pharmacological underpinnings of social behavior in a nonhuman primate species that demonstrates a repertoire of complex behavior (e.g., aggression or affiliative behavior) may provide insights into novel medication approaches aimed at restoring social deficits. Specifically, squirrel monkeys (Samiri boliviensis) emit a rich array of vocalizations that provide information on socio‐emotional and behavioral states. These vocalizations often co‐occur with readily observable behaviors that are easily quantifiable, permitting analyses of various aspects of social behavior. Previous studies have indicated that affiliative, or prosocial, vocalizations (pulsed calls and chucks) and behavior (huddling) may be modulated by serotonin 2A (5HT2A) receptors. To begin to understand how 5HT2A receptor activation influences social behavior, we examined the effects of R‐(‐)‐2,5‐dimethoxy‐4‐iodoamphetamine (DOI), a potent and moderately selective 5HT2A agonist, on affiliative vocalizations and observable behavior in nonhuman primates. Pair‐housed squirrel monkeys (2 males, 2 females) were transferred to an observation chamber outside of the colony and vocalizations and huddling were recorded during test sessions. Saline or DOI (0.01 or 0.06 mg/kg, IM) was administered prior to 30 min sessions. Results show that vocalizations, in particular pulsed calls, were increased following administration of 0.01 mg/kg DOI (438 ± 28) relative to saline (190.5 ± 21.5); a higher dose of 0.06 mg/kg DOI elicited a number of vocalizations that were not different from saline (201.5 ± 88.5). Frequency of huddling was unaffected by saline or DOI administration, however, increases in general activity were observed following DOI administration at both doses in comparison to saline. A preliminary examination of potential sex differences suggests that there were no differences between males and females in huddling or total number of vocalizations, though males produced more alarm calls at the highest dose of DOI tested. These data suggest that 5HT2A receptor activation is sufficient for increasing affiliative vocalizations, but may not change other indices of prosocial behavior, such as huddling. Future studies will expand the list of behaviors captured to include positional analyses of each subject, as well as evaluating the contribution of other 5HT receptors to specific dimensions of prosocial behavior.Support or Funding InformationResearch support provided by R01DA048150 (SJK).

Cafeteria‐style feeding trials provide new insights into the diet and nutritional strategies of the black snub‐nosed monkey (Rhinopithecus strykeri): Implications for conservation

Anthropogenic changes and fragmentation of natural habitats often exert a negative effect on resource availability and distribution, and the nutritional ecology and feeding behavior of nonhuman primates. The goals of this study are to examine food choice and to identify the nutritional profile of foods consumed by the Critically Endangered black snub-nosed monkey (Rhinopithecus strykeri). To accomplish our study goals, we presented cafeteria-style feeding trials of fresh food items collected in the home range of wild black snub-nosed monkeys to the only two captive R. strykeri, and compared the nutritional profiles of the leafy foods (buds, young, and mature leaves, 100 i23tems from 70 plant species) selected with those avoided (54 items from 48 plant species). Overall, the results indicate that captive R. strykeri selected foods that were higher in moisture (Mo; 77.7%), crude protein (CP; 21.2%), total nonstructural carbohydrates (TNC; 34.9%), and phosphorus (P; 0.37%) while tending to avoid foods with a neutral detergent fiber (NDF) content of greater than 46.8%. Leaves collected in autumn and selected by the monkeys were characterized by a slightly higher amount of metabolizable energy (ME) than those rejected (1,350 kJ/100 g vs. 1,268 kJ/100 g). In contrast, the protein content of foods collected and consumed during the spring was greater (22.9%) than in autumn (16.4%). Random Forests modeling, an ensemble learning method, indicated that the proportion of Mo, NDF, ME, CP, P, and TNC were among the most important factors in predicting which items were consumed by the captive R. strykeri during spring and autumn. On the basis of the nutritional profile of foods consumed across the two seasons, we identified 18 nutrient-rich native plant species that we recommend for use in ex- and in-situ conservation management and reforestation programs to provide long-term access to a nutritionally adequate diet.

AVPR1A variation is linked to gray matter covariation in the social brain network of chimpanzees.

The vasopressin system has been implicated in the regulation of social behavior and cognition in humans, nonhuman primates and other social mammals. In chimpanzees, polymorphisms in the vasopressin V1a receptor gene (AVPR1A) have been associated with social dimensions of personality, as well as to responses to sociocommunicative cues and mirror self-recognition. Despite evidence of this association with social cognition and behavior, there is little research on the neuroanatomical correlates of AVPR1A variation. In the current study, we tested the association between AVPR1A polymorphisms in the RS3 promotor region and gray matter covariation in chimpanzees using magnetic resonance imaging and source-based morphometry. The analysis identified 13 independent brain components, three of which differed significantly in covariation between the two AVPR1A genotypes (DupB-/- and DupB+/-; P < .05). DupB+/- chimpanzees showed greater covariation in gray matter in the premotor and prefrontal cortex, basal forebrain, lunate and cingulate cortex, and lesser gray matter covariation in the superior temporal sulcus and postcentral sulcus. Some of these regions were previously found to differ in vasopressin and oxytocin neural fibers between nonhuman primates, and in AVPR1A gene expression in humans with different RS3 alleles. This is the first report of an association between AVPR1A and gray matter covariation in nonhuman primates, and specifically links an AVPR1A polymorphism to structural variation in the social brain network. These results further affirm the value of chimpanzees as a model species for investigating the relationship between genetic variation, brain structure and social cognition with relevance to psychiatric disorders, including autism.

Variation in the μ-opioid receptor gene (OPRM1) and experiences of felt security in response to a romantic partner's quarrelsome behavior.

Research suggests that endogenous opioids play a key role in the creation and maintenance of attachment bonds. Opioids acting at the μ-opioid receptor mediate reward and analgesia and are thus thought to underlie feelings of comfort and warmth experienced in the presence of close others. Disruption of μ-opioidergic activity increases separation distress in animals, suggesting that low opioid states may contribute to social pain. Accordingly, a functional μ-opioid receptor (OPRM1) polymorphism (C77G in primates, A118G in humans) affecting opioidergic signaling has been associated with separation distress and attachment behavior in nonhuman primates, and social pain sensitivity in humans. However, no research has examined the effects of this polymorphism on socioemotional experience, and specifically felt security, in daily interactions between romantic partners. Using an event-contingent recording method, members of 92 cohabiting romantic couples reported their felt security and quarrelsome behavior in daily interactions with each other for 20 days. Consistent with prior work, findings suggested that, relative to AA homozygotes, G allele carriers were more sensitive to their partners' self-reported quarrelsome behaviors (e.g., criticism), showing a greater decline in felt security when their partners reported higher quarrelsome behavior than usual. This is the first study to link variation in OPRM1 with felt security toward romantic partners in everyday social interactions. More generally, this research supports the theory that the attachment system incorporated evolutionarily primitive pain-regulating opioidergic pathways. We also discuss implications of this work for understanding of differential vulnerability to health risks posed by social stress.

Maternal valproic acid exposure leads to neurogenesis defects and autism-like behaviors in non-human primates

Despite the substantial progress made in identifying genetic defects in autism spectrum disorder (ASD), the etiology for majority of ASD individuals remains elusive. Maternal exposure to valproic acid (VPA), a commonly prescribed antiepileptic drug during pregnancy in human, has long been considered a risk factor to contribute to ASD susceptibility in offspring from epidemiological studies in humans. The similar exposures in murine models have provided tentative evidence to support the finding from human epidemiology. However, the apparent difference between rodent and human poses a significant challenge to extrapolate the findings from rodent models to humans. Here we report for the first time the neurodevelopmental and behavioral outcomes of maternal VPA exposure in non-human primates. Monkey offspring from the early maternal VPA exposure have significantly reduced NeuN-positive mature neurons in prefrontal cortex (PFC) and cerebellum and the Ki67-positive proliferating neuronal precursors in the cerebellar external granular layer, but increased GFAP-positive astrocytes in PFC. Transcriptome analyses revealed that maternal VPA exposure disrupted the expression of genes associated with neurodevelopment in embryonic brain in offspring. VPA-exposed juvenile offspring have variable presentations of impaired social interaction, pronounced stereotypies, and more attention on nonsocial stimuli by eye tracking analysis. Our findings in non-human primates provide the best evidence so far to support causal link between maternal VPA exposure and neurodevelopmental defects and ASD susceptibility in humans.

Assessing behavior and cognition in rodents, nonhuman primates, and humans: where are the limits of translation? .

New psychopharmacological treatments are needed for affective and nonaffective psychoses, especially for the associated negative and cognitive symptoms. Earlier developments mostly failed, probably partly because of limitations in behavioral models used for validation. Now, deeper understanding of the genetics underlying disease pathogenesis and progress in genetic engineering will generate many rodent models with increased construct validity. To improve these models’ translational value, we need complementary data from nonhuman primates. We also have to improve and streamline behavioral test systems to cope with increased demand. Here, we propose a comprehensive neurocognitive test battery that should overcome the disadvantages of single tests and yield cognitive/behavioral profiles for modeling subsets of patient symptoms. Further, we delineate a concept for classifying disease-relevant cognitive endophenotypes to balance between face and construct validity and clinical diagnostics. In summary, this review discusses new concepts and the limitations and future potential of translational research on cognition in psychiatry.

Influence of cranial radiation by high-energy protons on the visuo-motor behavior of nonhuman primates

The visually driven instrumental conditioning on a one monkey (Macaca mulatta) was conducted after single-dose cranial irradiation with high-energy protons. The monkey executed saccades toward the visual stimuli and then performed the movement with ipsilateral hand correspondingly to their location in a right or left visual hemifield. The rate of correct responses with dominant right hand exceeded the rate of such responses with left hand and decreased briefly two months after irradiation. Then a month later, the rate of correct right-hand responses returned to the level before irradiation. No significant dynamics was revealed for the rate of correct left-hand responses. The proton irradiation effect on right-hand responses suggests possible short-term disturbances in the eye-hand coordination for right handedness while the visual perception remains resistant.