Adult Common Marmosets Research Articles

Comparative transcriptomics reveals human-specific cortical features.

The cognitive abilities of humans are distinctive among primates, but their molecular and cellular substrates are poorly understood. We used comparative single-nucleus transcriptomics to analyze samples of the middle temporal gyrus (MTG) from adult humans, chimpanzees, gorillas, rhesus macaques, and common marmosets to understand human-specific features of the neocortex. Human, chimpanzee, and gorilla MTG showed highly similar cell-type composition and laminar organization as well as a large shift in proportions of deep-layer intratelencephalic-projecting neurons compared with macaque and marmoset MTG. Microglia, astrocytes, and oligodendrocytes had more-divergent expression across species compared with neurons or oligodendrocyte precursor cells, and neuronal expression diverged more rapidly on the human lineage. Only a few hundred genes showed human-specific patterning, suggesting that relatively few cellular and molecular changes distinctively define adult human cortical structure.

Functional Cardiovascular Characterization of the Common Marmoset (Callithrix jacchus).

Appropriate cardiovascular animal models are urgently needed to investigate genetic, molecular, and therapeutic approaches, yet the translation of results from the currently used species is difficult due to their genetic distance as well as their anatomical or physiological differences. Animal species that are closer to the human situation might help to bridge this translational gap. The common marmoset (Callithrix jacchus) is an interesting candidate to investigate certain heart diseases and cardiovascular comorbidities, yet a basic functional characterization of its hemodynamic system is still missing. Therefore, cardiac functional analyses were performed by utilizing the invasive intracardiac pressure-volume loops (PV loop) system in seven animals, magnetic resonance imaging (MRI) in six animals, and echocardiography in five young adult male common marmosets. For a direct comparison between the three methods, only data from animals for which all three datasets could be acquired were selected. All three modalities were suitable for characterizing cardiac function, though with some systemic variations. In addition, vena cava occlusions were performed to investigate the load-independent parameters collected with the PV loop system, which allowed for a deeper analysis of the cardiac function and for a more sensitive detection of the alterations in a disease state, such as heart failure or certain cardiovascular comorbidities.

Bacterial Cholecystitis and Cholangiohepatitis in Common Marmosets (Callithrix Jacchus).

The common marmoset (Callithrix jacchus), a New World NHP, has emerged as important animal model in multiple areas of translational biomedical research. The quality of translational research in marmosets depends on early diagnosis, treatment, and prevention of their spontaneous diseases. Here, we characterize an outbreak of infectious cholangiohepatitis that affected 7 adult common marmosets in a single building over a 10-mo period. Marmosets presented for acute onset of lethargy, dull mentation, weight loss, dehydration, hyporexia, and hypothermia. Blood chemistries at presentation revealed markedly elevated hepatic and biliary enzymes, but mild neutrophilia was detected in only 1 of the 7. Affected marmosets were unresponsive to rigorous treatment and died or were euthanized within 48 h of presentation. Gross and histopathologic examinations revealed severe, necrosuppurative cholangiohepatitis and proliferative cholecystitis with bacterial colonies and an absence of gallstones. Perimortem and postmortem cultures revealed single or dual isolates of Escherichia coli and Pseudomonas aeruginosa. Other postmortem findings included bile duct hyperplasia, periportal hepatitis, bile peritonitis, ulcerative gastroenteritis, and typhlitis. Environmental contamination of water supply equipment with Pseudomonas spp. was identified as the source of infection, but pathogenesis remains unclear. This type of severe, infectious cholangiohepatitis with proliferative cholecystitis with Pseudomonas spp. had not been reported previously in marmosets, and we identified and here describe several contributing factors in addition to contaminated drinking water.

Evaluation of Anesthetic and Cardiorespiratory Effects after Intramuscular Administration of Three Different Doses of Telazol® in Common Marmosets (Callithrix jacchus).

Marmosets' small body size makes anesthesia challenging. Ideally, small volumes of drugs should be administered intramuscularly (i.m.). In addition, dose-dependent sedation and anesthesia are desirable properties for sedatives and anesthetics in marmosets. Telazol® (tiletamine and zolazepam) is highly concentrated, allowing the use of small injection volumes and dose-dependent sedation and anesthesia. A randomized, blinded study with crossover design in ten healthy adult common marmosets (Callithrix jacchus) was performed to evaluate the anesthetic and cardiorespiratory effects of three doses of i.m. Telazol® (respectively, 5, 10, and 15 mg/kg). Depth of anesthesia, cardiorespiratory effects, and induction, immobilization, and recovery times were determined. A significant difference was observed in immobilization time between 5 and 15 mg/kg of Telazol®. In addition, 15 mg/kg of Telazol® resulted in increased recovery times compared to 5 mg/kg. The cardiorespiratory effects during the first 45 min of immobilization were within clinically acceptable limits. The pedal withdrawal reflex was the best indicator of the anesthetic depth.

Hepatic steatosis, a lesion reported in captive aged common marmosets.

Hepatic steatosis, also known as fatty liver, is a spontaneous lesion caused by the abnormal accumulation of triglycerides within hepatocytes that has been described in different laboratory-housed nonhuman primate species. Aging is considered a risk factor in the progression of this lesion in humans and captive rhesus macaques. Hepatic steatosis has been reported in sexually mature adult and aged-adult captive common marmosets. Macroscopic changes in the liver may be evident in advanced stages of this condition and are characterized by hepatomegaly with multifocal to coalescing to regionally extensive pale-tan to yellow, soft foci throughout the hepatic lobes. Biochemical abnormalities in these cases include significantly increased levels in triglycerides, insulin, and γ-glutamyltransferase (GGT). Definitive diagnosis is by histopathology and demonstration of lipid accumulation within hepatocytes. Histopathology is characterized by large coalescing areas of periacinar to periportal microvesicular steatosis mixed with clusters of macrovesicular steatosis, and variable degrees of lobular inflammation. Vacuolated hepatocytes containing intracytoplasmic lipid material is demonstrated by positive staining to Sudan IV and/or Oil red-O.

The Effect of Body Region on Hair Cortisol Concentration in Common Marmosets (Callithrix jacchus)

Common marmosets (Callithrix jacchus) are a valuable research model for the study of neuroscience and the biologic impact of aging due to their adaptivity, physiologic characteristics, and ease of handling for experimental manipulations. Quantification of cortisol in hair provides a noninvasive, retrospective biomarker of hypothalamics-pituitary-adrenal (HPA) axis activity and information on animal wellbeing, including responses to environmental and social stimuli. To obtain valid and reliable measurements of long-term HPA activity, we investigated the variability of cortisol concentration in the hair depending on the body region of marmosets. Hair was collected from the back and tail of 9 adult common marmosets during annual health screenings (male n = 3; female n = 6) and these samples were analyzed for cortisol via methanol extraction and enzyme immunoassay. We found that hair cortisol concentration differed between the tail and back regions, with the tail samples having a significantly higher cortisol concentration. These results indicate intraindividual and interindividual comparisons of hair cortisol concentration should use hair obtained from the same body region in marmosets.

Pharmacokinetics of Buprenorphine and Sustained-release Buprenorphine in Common Marmosets (Callithrix jacchus).

Buprenorphine is an essential component of analgesic protocols in common marmosets (Callithrix jacchus). The use of buprenorphine HCl (BUP) and sustained-release buprenorphine (BSR) formulations has become commonplace in this species, but the pharmacokinetics have not been evaluated. Healthy adult (age, 2.4 to 6.8 y; 6 female and 6 male) common marmosets were enrolled in this study to determine the pharmacokinetic parameters, plasma concentration-time curves, and any apparent adverse effects of these compounds. Equal numbers of each sex were randomly assigned to receive BUP (0.02 mg/kg IM) or BSR (0.2 mg/kg SC), resulting in peak plasma concentrations (mean ± 1 SD) of 15.2 ± 8.1 and 2.8 ± 1.2 ng/mL, terminal phase t1/2 of 2.2 ± 1.0 and 32.6 ± 9.6 h, and AUC0-last of 16.1 ± 3.7 and 98.6 ± 42.7 ng × h/mL. The plasma concentrations of buprenorphine exceeded the proposed minimal therapeutic threshold (0.1 ng/mL) at 5 and 15 min after BUP and BSR administration, showing that both compounds are rapid-acting, and remained above that threshold through the final time points of 8 and 72 h. Extrapolation of the terminal elimination phase of the mean concentration-time curves was used to develop the clinical dosing frequencies of 6 to 8 h for BUP and 3.0 to 3.5 d for BSR. Some adverse effects were observed after the administration of BUP to common marmosets in this study, thus mandating judicious use in clinical practice. BSR provided a safe, long-acting option for analgesia and therefore can be used to refine analgesic protocols in this species.

The long-term impact of infant rearing background on the behavioural and physiological stress response of adult common marmosets (Callithrix jacchus)

Although triplet litters are increasing in captive colonies of common marmosets, parents can rarely rear more than two infants without human intervention. There is however much evidence that early life experience, including separation from the family, can influence both vulnerability and resilience to stress. The current study investigated the behavioural and hypothalamic pituitary adrenal (HPA) axis response to the routine stressor of capture and weighing in adult common marmosets (Callithrix jacchus), reared as infants under 3 different conditions: family reared twins (n = 6 individuals), family reared animals from triplet litters where only 2 remain (2stays: n = 8) and triplets receiving supplementary feeding from humans (n = 7). In the supplementary feeding condition, infants remained in contact with each other when they were removed from the family. There were no significant differences (P > 0.5) in cortisol level or behaviour between the rearing conditions. In all conditions, salivary cortisol decreased from baseline to post capture, which was accompanied by increases in agitated locomotion. Familyreared 2stays demonstrated significant cortisol decreases from baseline to post capture (post 5 min.: P = 0.005; post 30 min.: P = 0.018), compared to the other conditions. Family reared twins displayed significantly more behavioural changes following the stressor than the other conditions, including significant increases in scent marking (post 5 min. and post 30 min.: P = 0.028) and significant decreases in inactive alert (post 5 min.: P = 0.042), calm locomotion (post 5 min.: P = 0.028; post 30 min.: P = 0.046) and proximity to partner (post 5 min.: P = 0.046). There were increases in behaviour suggesting reduced anxiety, including significantly more exploration post capture in supplementary fed triplets (post 5 min.: P = 0.041), and significantly more foraging post capture in family reared 2stays (post 5 min. .: P = 0.039). However, as differences between rearing conditions were minimal, supplementary feeding of large litters of marmosets at this facility did not have a major effect on stress vulnerability, suggesting that this rearing practice may be the preferred option if human intervention is necessary to improve the survival of large litters.

Personality and lateralization in common marmosets (Callithrix jacchus)

Specialization of the left and right hemispheres to control behavioural responses may represent one of the mechanisms underlying individual differences in personality structure, as well as the preferential use of one hand. The present study investigated the relationship between personality and hand preference in common marmosets (Callithrix jacchus), a little New World monkey that presents highly consistent and stable individual hand preferences for simple reaching. To address this issue, data on 56 different behaviours from the species’ behavioural repertoire were measured in 10 different laboratory tests and during observations under social conditions on 16 adult common marmosets. Stable behavioural variables were aggregated a priori into 13 personality traits. Exploratory Factor Analysis (EFA) on personality traits was carried out to verify the presence of major personality factors, and their relationship with direction and strength of individual hand preferences was assessed by multiple regression, taking into account sex and age of the subjects. The largest number of species-specific behaviours so far investigated in this species was taken into account and robust temporal stability between two testing periods was verified. We confirm that common marmosets are characterized by specific and stable personality profiles. A single personality factor, accounting for about 38% of the total variance, was found by EFA, that describes the interest towards unusual and new experiences and resembles the human Openness domain. The strength of the hand preference was found to be predicted by this personality factor, that we named Inquisitiveness. Present results highlight common marmoset as a useful primate model for the study of the relationship between personality and lateralization.

Long-lasting vocal plasticity in adult marmoset monkeys.

Humans exhibit a high level of vocal plasticity in speech production, which allows us to acquire both native and foreign languages and dialects, and adapt to local accents in social communication. In comparison, non-human primates exhibit limited vocal plasticity, especially in adulthood, which would limit their ability to adapt to different social and environmental contexts in vocal communication. Here, we quantitatively examined the ability of adult common marmosets (Callithrix jacchus), a highly vocal New World primate species, to modulate their vocal production in social contexts. While recent studies have demonstrated vocal learning in developing marmosets, we know much less about the extent of vocal learning and plasticity in adult marmosets. We found, in the present study, that marmosets were able to adaptively modify the spectrotemporal structure of their vocalizations when they encountered interfering sounds. Our experiments showed that marmosets shifted the spectrum of their vocalizations away from the spectrum of the interfering sounds in order to avoid the overlap. More interestingly, we found that marmosets made predictive and long-lasting spectral shifts in their vocalizations after they had experienced a particular type of interfering sound. These observations provided evidence for directional control of the vocalization spectrum and long-term vocal plasticity by adult marmosets. The findings reported here have important implications for the ability of this New World primate species in voluntarily and adaptively controlling their vocal production in social communication.

Comparing Hierarchical Patterns of Constraint and Functional Trait Complexes in the Primate Shoulder and Hip Regions Among New World and Old‐World Monkeys

The scapula shares developmental and functional relationships with the basicranium, clavicle, vertebral column, and humerus. Its characteristics are also analogous with the pelvis as a limb girdle. Despite these relationships, in studies of primate shoulder evolution, the scapula is often examined in isolation. However, genetic covariances underlie functional and developmental relationships that result in non‐independent evolution of the scapula from these other skeletal elements. To understand evolution in the scapula, then, accurate models of trait responses to selection must account for the constraints imposed by these covariances.In this study, we work from the position that genetic covariances among morphological traits of the shoulder girdle and basicranium reflect the developmental and functional relationships between them. We use this premise to examine if the genetic covariances constrain the ability of these elements to respond to selection. Due to the developmental and functional parallels among limb girdles, pelvic dimensions are included in our analysis. We obtained cranial and postcranial linear dimensions from a sample of 105 adult common marmosets (Callithrix jacchus) and 66 adult macaques (Macaca mulatta). These measurements are associated with the basicranium, the shoulder, and the pelvis. Measurements were mean‐standardized prior to analysis. We calculated the evolvability and conditional evolvability of these traits in R following the equations of Hansen and Houle; these indices were estimated using 1000 simulated random selection gradients. Greater constraint among traits is indicated by lower evolvability. Lower conditional evolvability reflects constraint on a trait when all other traits' means did not change under selection. Analyses were performed on the following configuration of traits: shoulder girdle and basicranium, shoulder and pelvic girdles, and basicranium and pelvic girdle. Differences in evolvability measures were evaluated by recomputing each value for 1000 iterations of the bootstrapped sample, and performing a pairwise comparison of the bootstrapped values.Our results show that evolvability indices, especially conditional evolvability, are lower among traits of the shoulder girdle and basicranium when compared to those of the shoulder girdle and pelvis, and the basicranium and pelvis. This indicates a tiered pattern of constraint among anatomical regions, with a privileged relationship existing between the basicranium and shoulder girdle. These results are consistent for both macaques and marmosets, suggesting a deep phylogenetic origin among primates for genetic covariances among these anatomical regions. We conclude that the basicranium and shoulder girdle constrain each other in response to directional selection, forming a functional trait complex, and has important implications for models of shoulder evolution.Support or Funding InformationThis research is supported by a National Science Foundation Doctoral Dissertation Improvement Grant (NSF BCS‐1825995).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Animal models of synucleinopathies: prion-like propagation of alpha-synuclein in wild-type animals

Accumulation of insoluble alpha-synuclein (αS) is a pathological hallmark of some progressive neurodegenerative diseases including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, collectively termed synucleinopathies. In diseased brain, αS forms β-sheet-rich amyloid fibrils and it is accumulated in neurons or glial cells. A growing body of evidence suggests that spreading of αS pathology occur by prion-like propagation mechanisms. Our study revealed that intracerebral injection of synthetic αS amyloid fibrils into wild-type mice induced prion-like propagation of αS pathology at 1 month post injection, while injection of soluble αS did not induce αS pathology. Furthermore, injection of αS amyloid fibrils into αS knockout mice failed to induce any pathologies. We also have demonstrated that intracerebral injection of αS amyloid fibrils into small primates, adult common marmosets, resulted in spreading of αS pathologies and loss of TH-positive neurons. These in vivo experiments clearly indicate that αS amyloid fibrils has prion-like properties and it propagates through neural networks. The underlying mechanisms of αS propagation are poorly understood, however, αS propagation model animals would be useful in elucidating pathogenetic mechanisms and developing disease-modifying drugs for sporadic synucleinopathies.

Maintenance of bone mass despite estrogen depletion in female common marmoset monkeys (Callithrix jacchus).

Estrogen depletion leads to bone loss in almost all mammals with frequent regular ovarian cycles. However, subordinate adult female common marmosets (Callithrix jacchus) undergo socially induced anovulation and hypoestrogenism without clinically apparent adverse skeletal consequences. Thus, we speculated that this non human primate might have evolved a mechanism to avoid estrogen-depletion bone loss. To test this possibility, we performed three experiments in which lumbar-spine (L5-L6) bone mineral content (BMC) and density (BMD) were assessed using dual-energy X-ray absorptiometry: (i) cross-sectionally in 13 long-term ovariectomized animals and 12 age- and weight-matched controls undergoing ovulatory cycles; (ii) longitudinally in 12 animals prior to, 3-4 and 6-7 months following ovariectomy (ovx), and six controls; and (iii) cross-sectionally in nine anovulatory subordinate and nine dominant females. In Experiments 1 and 3, plasma estradiol and estrone concentrations were measured and uterine dimensions were obtained by ultrasound in a subset of animals as a marker of functional estrogen depletion. Estrogen levels, uterine trans-fundus width, and uterine dorso-ventral diameter were lower in ovariectomized and subordinate females than in those undergoing ovulatory cycles. However, no differences were found in L5-L6 BMC or BMD. These results indicate that estrogen depletion, whether surgically or socially induced, is not associated with lower bone mass in female common marmosets. Thus, this species may possess unique adaptations to avoid bone loss associated with estrogen depletion.

Accurate motor mapping in awake common marmosets using micro-electrocorticographical stimulation and stochastic threshold estimation

Objective. Motor map has been widely used as an indicator of motor skills and learning, cortical injury, plasticity, and functional recovery. Cortical stimulation mapping using epidural electrodes is recently adopted for animal studies. However, several technical limitations still remain. Test-retest reliability of epidural cortical stimulation (ECS) mapping has not been examined in detail. Many previous studies defined evoked movements and motor thresholds by visual inspection, and thus, lacked quantitative measurements. A reliable and quantitative motor map is important to elucidate the mechanisms of motor cortical reorganization. The objective of the current study was to perform reliable ECS mapping of motor representations based on the motor thresholds, which were stochastically estimated by motor evoked potentials and chronically implanted micro-electrocorticographical (µECoG) electrode arrays, in common marmosets. Approach. ECS was applied using the implanted µECoG electrode arrays in three adult common marmosets under awake conditions. Motor evoked potentials were recorded through electromyographical electrodes implanted in upper limb muscles. The motor threshold was calculated through a modified maximum likelihood threshold-hunting algorithm fitted with the recorded data from marmosets. Further, a computer simulation confirmed reliability of the algorithm. Main results. Computer simulation suggested that the modified maximum likelihood threshold-hunting algorithm enabled to estimate motor threshold with acceptable precision. In vivo ECS mapping showed high test-retest reliability with respect to the excitability and location of the cortical forelimb motor representations. Significance. Using implanted µECoG electrode arrays and a modified motor threshold-hunting algorithm, we were able to achieve reliable motor mapping in common marmosets with the ECS system.

Medullary Conus Topography in White-Tufted-Ear-Marmoset (Callithrix jacchus)

Background: The common marmoset (Callithrix jacchus) belongs to the family Cebidae and Subfamily Callitrichinae, a group formed by the smallest anthropoid primates. It is a very common species and adapts easily to captivity, an aspect that encourages the clandestine capture of these animals and makes them susceptible to wounds resulting from clandestine rearing and inadequate management, so that studies to understand the species are extremely important. With the objective of supplying anatomic bases for the practice of epidural anesthetic, data were studied regarding the topography of the common marmoset (Callithrix jacchus).Materials, Methods & Results: The study was carried out at the Laboratory of Veterinary Anatomy at the Federal University of Campina Grande (UFCG), PA, Brazil. Ten adult common marmosets (Callithrix jacchus) were used, 5 males and 5 females, with different causes of death. A round workbench magnifying lamp was used to better visualize the dissecation field. Number 15 scalpel blades, surgical pincers and scissors were used to dissect. After fixing in 10% formaldehyde aqueous solution, dissecation was made along the mid dorsal line, from the cranial thoracic region to the tail base to expose the vertebral arches and measure the intervertebral spaces. The vertebral arches were removed, and consequently the spinal dura mater was exposed, that was sectioned longitudinally to expose the spinal chord and identify the lumbar intumescence, the conus medullaris and the cauda equina. The length of the conus medullaris was measured and its skeletopy was established. The body and tail length data were submitted to analysis of variance and the means were compared by the Tukey test at 5% probability. The mean value of the conus medullaris length was 1.4 cm, while the anatomic location of the conus medullaris varied slightly among the animals, but did not pass the limit between L3 for the base and L6 for the apex. On average, the lumbosacral space measured 3.03 mm, that is sufficient to introduce a needle similar to that used in syringes for insulin injection. The results of this study suggest the lumbarsacral space as location for epidural anesthetic application in Callithrix jacchus, at a safe point situated in the center of an isosceles triangle, the base of which is found when a line is drawn from one side of the pelvis to the other, and the apex corresponds the spinal process of the first sacral vertebra.Discussion: The anatomic location of the conus medullaris is different compared to two other primate species, the red handed tamarin (Saguinus midas), in which the cone base was registered at L4 and the apex at S2, and the common squirrel monkey (Saimiri sciureus) where the conus medullaris base occurs at L7-8 and the apex at S3 or Cc1. However, some similarities with other mammal groups were observed in the conus medullaris topography, such as the black-striped capuchin (Sapajus libidinosus). The mean conus medullaris length of the species Callithrix jacchus of 1.4 cm was close to that observed in the coypu, capuchin monkey and sloth, and significantly smaller than the means obtained for the red handed tamarin and common squirrel monkey and other non-primate mammals reported in the literature. The lumbosacral space is the location indicated for epidural anesthesia in Callithrix jacchus, that has also been indicated for other wild mammals such as the black-striped capuchin monkey (Sapajus libidinosus), the maned wolf (Chrysocyon brachyurus), the tayra (Eira barbara), the giant otter (Pteronura brasiliensis), the crab-eating racoon (Procyon cancrivorus) and the coypu (Myocastor coypus).

Common marmoset (Callithrix jacchus) personality.

Increasing evidence suggests that personality structure differs between species, but the evolutionary reasons for this variation are not fully understood. We built on earlier research on New World monkeys to further elucidate the evolution of personality structure in primates. We therefore examined personality in 100 family-reared adult common marmosets (Callithrix jacchus) from 3 colonies on a 60-item questionnaire. Principal components analyses revealed 5 domains that were largely similar to those found in a previous study on captive, ex-pet, or formerly laboratory-housed marmosets that were housed in a sanctuary. The interrater reliabilities of domain scores were consistent with the interrater reliabilities of domain scores found in other species, including humans. Four domainsdmdash;conscientiousness, agreeableness, inquisitiveness, and assertiveness-resembled personality domains identified in other nonhuman primates. The remaining domain, patience, was specific to common marmosets. We used linear models to test for sex and age differences in the personality domains. Males were lower than females in patience, and this difference was smaller in older marmosets. Older marmosets were lower in inquisitiveness. Finally, older males and younger females had higher scores in agreeableness than younger males and older females. These findings suggest that cooperative breeding may have promoted the evolution of social cognition and influenced the structure of marmoset prosocial personality characteristics. (PsycINFO Database Record

Use of human methylation arrays for epigenome research in the common marmoset (Callithrix jacchus)

We examined the usefulness of commercially available DNA methylation arrays designed for the human genome (Illumina HumanMethylation450 and MethylationEPIC) for high-throughput epigenome analysis of the common marmoset, a nonhuman primate suitable for research on neuropsychiatric disorders. From among the probes on the methylation arrays, we selected those available for the common marmoset. DNA methylation data were obtained from genomic DNA extracted from the frontal cortex and blood samples of adult common marmosets as well as the frontal cortex of neonatal marmosets. About 10% of the probes on the arrays were estimated to be useful for DNA methylation assay in the common marmoset. Strong correlations existed between human and marmoset DNA methylation data. Illumina methylation arrays are useful for epigenome research using the common marmoset.

Whole-brain metallomic analysis of the common marmoset (Callithrix jacchus).

Despite the importance of transition metals for normal brain function, relatively little is known about the distribution of these elemental species across the different tissue compartments of the primate brain. In this study, we employed laser ablation-inductively coupled plasma-mass spectrometry on PFA-fixed brain sections obtained from two adult common marmosets. Concurrent cytoarchitectonic, myeloarchitectonic, and chemoarchitectonic measurements allowed for identification of the major neocortical, archaecortical, and subcortical divisions of the brain, and precise localisation of iron, manganese, and zinc concentrations within each division. Major findings across tissue compartments included: (1) differentiation of white matter tracts from grey matter based on manganese and zinc distribution; (2) high iron concentrations in the basal ganglia, cortex, and substantia nigra; (3) co-localization of high concentrations of iron and manganese in the primary sensory areas of the cerebral cortex; and (4) high manganese in the hippocampus. The marmoset has become a model species of choice for connectomic, aging, and transgenic studies in primates, and the application of metallomics to these disciplines has the potential to yield high translational and basic science value.

Functional Connectivity Hubs and Networks in the Awake Marmoset Brain.

In combination with advances in analytical methods, resting-state fMRI is allowing unprecedented access to a better understanding of the network organization of the brain. Increasing evidence suggests that this architecture may incorporate highly functionally connected nodes, or “hubs”, and we have recently proposed local functional connectivity density (lFCD) mapping to identify highly-connected nodes in the human brain. Here, we imaged awake nonhuman primates to test whether, like the human brain, the marmoset brain contains FC hubs. Ten adult common marmosets (Callithrix jacchus) were acclimated to mild, comfortable restraint using individualized helmets. Following restraint training, resting BOLD data were acquired during eight consecutive 10 min scans for each subject. lFCD revealed prominent cortical and subcortical hubs of connectivity across the marmoset brain; specifically, in primary and secondary visual cortices (V1/V2), higher-order visual association areas (A19M/V6[DM]), posterior parietal and posterior cingulate areas (PGM and A23b/A31), thalamus, dorsal and ventral striatal areas (caudate, putamen, lateral septal nucleus, and anterior cingulate cortex (A24a). lFCD hubs were highly connected to widespread areas of the brain, and further revealed significant network-network interactions. These data provide a baseline platform for future investigations in a nonhuman primate model of the brain’s network topology.

Flibanserin-Stimulated Partner Grooming Reflects Brain Metabolism Changes in Female Marmosets.

Female sexual interest and arousal disorder is personally distressing for women. To better understand the mechanism of the candidate therapeutic, flibanserin, we determined its effects on an index of brain glucose metabolism. We hypothesized that chronic treatment with flibanserin would alter metabolism in brain regions associated with serotonergic function and female sexual behavior. In a crossover design, eight adult female common marmosets (Calithrix jacchus) received daily flibanserin or vehicle. After 7-12 weeks of treatment, the glucose metabolism radiotracer [(18) F]fluorodeoxyglucose (FDG) was administered to each female immediately prior to 30 minutes of interaction with her male pairmate, after which females were anesthetized and imaged by positron emission tomography. Whole-brain normalized images were analyzed with anatomically defined regions of interest. Whole-brain voxelwise mapping was used to explore treatment effects. Correlations were examined between alterations in metabolism and pairmate social grooming. Changes in metabolism associated with flibanserin were determined for dorsal raphe, medial prefrontal cortex (mPFC), medial preoptic area of hypothalamus (mPOA), ventromedial nucleus of hypothalamus, and field cornu ammonis 1 (CA1) of the hippocampus. In response to chronic flibanserin, metabolism in mPOA declined, and this reduction correlated with increases in pairmate grooming. A cluster of voxels in frontal cortico-limbic regions exhibited reduced metabolism in response to flibanserin and overlapped with a voxel cluster in which reductions in metabolism correlated with increases in pairmate grooming. Finally, reductions in mPOA metabolism correlated with increases in metabolism in a cluster of voxels in somatosensory cortex. Taken together, these results suggest that flibanserin-induced reductions in female mPOA neural activity increase intimate affiliative behavior with male pairmates.