Pairing status and stimulus type predict responses to audio playbacks in female titi monkeys

Some paired primates use complex, coordinated vocal signals to communicate within and between family groups. The information encoded within those signals is not well understood, nor is the intricacy of individuals’ behavioral and physiological responses to these signals. Considering the conspicuous nature of these vocal signals, it is a priority to better understand paired primates’ responses to conspecific calls. Pair-bonded titi monkeys (Plecturocebus cupreus) sing duets comprised of the male and female’s long call. Here, we use a playback study to assess female titi monkeys’ responses to different vocal stimuli based on the subject’s pairing status. Six adult female titi monkeys participated in the study at two timepoints—pre-pairing and post-pairing. At each timepoint, subjects underwent three distinct playbacks—control recording, male solo vocalization, and pair duet. Behaviors such as locomotion and vocalizations were scored during and after the playback, and cortisol and androgen values were assessed via a plasma blood sample. Female titi monkeys attended more to social signals compared to the control, regardless of pairing status. However, in the time immediately following any playback type, female titi monkeys trilled more and spent a greater proportion of time locomoting during pre-pairing timepoints (compared to post-pairing). Female titi monkeys’ behavioral responses to social audio stimuli, combined with subjects’ increases in cortisol and androgens as paired individuals, imply female titi monkeys attend and respond to social signals territorially

An Animal Model for Mammalian Attachment: Infant Titi Monkey (Plecturocebus cupreus) Attachment Behavior Is Associated With Their Social Behavior as Adults.

Close social bonds are integral for good health and longevity in humans and non-human primates (NHPs), yet we have very little understanding of the neurobiological differences between healthy and unhealthy relationships. Our current understanding of social bonding is grounded in Bowlby's theory of attachment. Work done with human infants and adult couples has suggested that attachment behavior developed in infancy remains stable through development into adulthood. Unfortunately, knowledge of the neurobiological correlates of attachment behavior has been limited due to a lack of animal models with both infant and adult attachments similar to humans. To address this, we measured behavioral responses to separation from their primary attachment figure in infant and adult titi monkeys (Plecturocebus cupreus). In Experiment 1, we tested for a linear relationship between the subject's response to separation as an infant and their response to separation as an adult. We found greater decreases in infant locomotor behavior in the presence, as opposed to absence, of their primary attachment figure to be indicative of decreased anxiety-like behavior in the presence, as opposed to absence, of their adult pair mates during a novelty response task. In Experiment 2, we increased our sample size, accounted for adverse early experience, and tested a different outcome measure, adult affiliative behavior. We hypothesized that the level of intensity of an infant's response to separation would explain affiliative behavior with their mate as an adult, but adverse early experience could change this relationship. When we compared infant response to separation to adult affiliative behavior during the first 6 months of their first adult pair bond, we observed a linear relationship for infants with typical early experience, but not for infants with adverse early experience. Infants with a greater change in locomotive behavior between the father and alone conditions were more affiliative with their first adult pair mate. These data support the use of titi monkeys as an appropriate animal model for further investigation of the neurobiology underlying attachment behavior

Nonapeptide Receptor Distributions in Promising Avian Models for the Neuroecology of Flocking

Collective behaviors, including flocking and group vocalizing, are readily observable across a diversity of free-living avian populations, yet we know little about how neural and ecological factors interactively regulate these behaviors. Because of their involvement in mediating a variety of social behaviors, including avian flocking, nonapeptides are likely mediators of collective behaviors. To advance the neuroecological study of collective behaviors in birds, we sought to map the neuroanatomical distributions of nonapeptide receptors in three promising avian models that are found across a diversity of environments and widely ranging ecological conditions: European starlings, house sparrows, and rock doves. We performed receptor autoradiography using the commercially available nonapeptide receptor radioligands, 125I-ornithine vasotocin analog and 125I-linear vasopressin antagonist, on brain tissue sections from wild-caught individuals from each species. Because there is known pharmacological cross-reactivity between nonapeptide receptor subtypes, we also performed a novel, competitive-binding experiment to examine the composition of receptor populations. We detected binding in numerous regions throughout the brains of each species, with several similarities and differences worth noting. Specifically, we report that all three species exhibit binding in the lateral septum, a key brain area known to regulate avian flocking. In addition, sparrows and starlings show dense binding in the dorsal arcopallium, an area that has received scant attention in the study of social grouping. Furthermore, our competitive binding results suggest that receptor populations in sparrows and starlings differ in the lateral septum versus the dorsal arcopallium. By providing the first comprehensive maps of nonapeptide receptors in European starlings, house sparrows, and rock doves, our work supports the future use of these species as avian models for neuroecological studies of collective behaviors in wild birds

Are Behavioral Effects of Early Experience Mediated by Oxytocin?

Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster), manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT) and arginine vasopressin (AVP), have long-lasting, often sexually dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN1–7 animals were handled once a day for post-natal days 1–7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1–7) displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation

Non-invasive Eye Tracking Methods for New World and Old World Monkeys

Eye-tracking methods measure what humans and other animals visually attend to in the environment. In nonhuman primates, eye tracking can be used to test hypotheses about how primates process social information. This information can further our understanding of primate behavior as well as offer unique translational potential to explore causes of or treatments for altered social processing as seen in people with neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. However, previous methods for collecting eye-tracking data in nonhuman primates required some form of head restraint, which limits the opportunities for research with respect to the number of or kinds of primates that can undergo an eye-tracking study. We developed a novel, noninvasive method for collecting eye tracking data that can be used both in animals that are difficult to restrain without sedation as well as animals that are of different ages and sizes as the box size can be adjusted. Using a transport box modified with a viewing window, we collected eye-tracking data in both New (Callicebus cupreus) and Old World monkeys (Macaca mulatta) across multiple developmental time points. These monkeys had the option to move around the box and avert their eyes from the screen, yet, they demonstrated a natural interest in viewing species-specific imagery with no previous habituation to the eye-tracking paradigm. Provided with opportunistic data from voluntary viewing of stimuli, we found that juveniles viewed stimuli more than other age groups, videos were viewed more than static photo imagery, and that monkeys increased their viewing time when presented with multiple eye tracking sessions. This noninvasive approach opens new opportunities to integrate eye-tracking studies into nonhuman primate research

Generation of Induced Pluripotent Stem Cells from the Prairie Vole

The vast majority of animals mate more or less promiscuously. A few mammals, including humans, utilize more restrained mating strategies that entail a longer term affiliation with a single mating partner. Such pair bonding mating strategies have been resistant to genetic analysis because of a lack of suitable model organisms. Prairie voles are small mouse-like rodents that form enduring pair bonds in the wild as well as in the laboratory, and consequently they have been used widely to study social bonding behavior. The lack of targeted genetic approaches in this species however has restricted the study of the molecular and neural circuit basis of pair bonds. As a first step in rendering the prairie vole amenable to reverse genetics, we have generated induced pluripotent stem cell (IPSC) lines from prairie vole fibroblasts using retroviral transduction of reprogramming factors. These IPSC lines display the cellular and molecular hallmarks of IPSC cells from other organisms, including mice and humans. Moreover, the prairie vole IPSC lines have pluripotent differentiation potential since they can give rise to all three germ layers in tissue culture and in vivo. These IPSC lines can now be used to develop conditions that facilitate homologous recombination and eventually the generation of prairie voles bearing targeted genetic modifications to study the molecular and neural basis of pair bond formation

Genetic polymorphisms and susceptibility to lung disease

Susceptibility to infection by bacterium such as Bacillus anthracis has a genetic basis in mice and may also have a genetic basis in humans. In the limited human cases of inhalation anthrax, studies suggest that not all individuals exposed to anthrax spores were infected, but rather, individuals with underlying lung disease, particularly asthma, sarcoidosis and tuberculosis, might be more susceptible. In this study, we determined if polymorphisms in genes important in innate immunity are associated with increased susceptibility to infectious and non-infectious lung diseases, particularly tuberculosis and sarcoidosis, respectively, and therefore might be a risk factor for inhalation anthrax. Examination of 45 non-synonymous polymorphisms in ten genes: p47phox (NCF1), p67phox (NCF2), p40phox (NCF4), p22phox (CYBA), gp91phox (CYBB), DUOX1, DUOX2, TLR2, TLR9 and alpha 1-antitrypsin (AAT) in a cohort of 95 lung disease individuals and 95 control individuals did not show an association of these polymorphisms with increased susceptibility to lung disease

Cross-Species Transmission of a Novel Adenovirus Associated with a Fulminant Pneumonia Outbreak in a New World Monkey Colony

Adenoviruses are DNA viruses that naturally infect many vertebrates, including humans and monkeys, and cause a wide range of clinical illnesses in humans. Infection from individual strains has conventionally been thought to be species-specific. Here we applied the Virochip, a pan-viral microarray, to identify a novel adenovirus (TMAdV, titi monkey adenovirus) as the cause of a deadly outbreak in a closed colony of New World monkeys (titi monkeys; Callicebus cupreus) at the California National Primate Research Center (CNPRC). Among 65 titi monkeys housed in a building, 23 (34%) developed upper respiratory symptoms that progressed to fulminant pneumonia and hepatitis, and 19 of 23 monkeys, or 83% of those infected, died or were humanely euthanized. Whole-genome sequencing of TMAdV revealed that this adenovirus is a new species and highly divergent, sharing <57% pairwise nucleotide identity with other adenoviruses. Cultivation of TMAdV was successful in a human A549 lung adenocarcinoma cell line, but not in primary or established monkey kidney cells. At the onset of the outbreak, the researcher in closest contact with the monkeys developed an acute respiratory illness, with symptoms persisting for 4 weeks, and had a convalescent serum sample seropositive for TMAdV. A clinically ill family member, despite having no contact with the CNPRC, also tested positive, and screening of a set of 81 random adult blood donors from the Western United States detected TMAdV-specific neutralizing antibodies in 2 individuals (2/81, or 2.5%). These findings raise the possibility of zoonotic infection by TMAdV and human-to-human transmission of the virus in the population. Given the unusually high case fatality rate from the outbreak (83%), it is unlikely that titi monkeys are the native host species for TMAdV, and the natural reservoir of the virus is still unknown. The discovery of TMAdV, a novel adenovirus with the capacity to infect both monkeys and humans, suggests that adenoviruses should be monitored closely as potential causes of cross-species outbreaks