Chapter 22 - The Marmoset as a Model for Visual Neuroscience

The common marmoset, Callithrix jacchus, is increasingly being used as the preferred nonhuman primate (NHP) model in biomedical research. Marmosets share severalphysiological and biological similarities with humans, as a Simiiformes species, and their use in research programs advances knowledge in several fields. Their unique characteristics, suchas their small size, high fecundity, and rapid growth, offer additional advances in laboratory settings. This article reviews the developments in experimental disease models using marmosetsbased on our experience at the Central Institute for Experimental Animals (CIEA) in Japan. The development of genetically modified marmoset models using advanced genome editing technology isattracting researchers, particularly in neuroscience-related fields. In parallel, various marmoset models of human diseases induced by surgery or drug administration have contributed topreclinical and translational studies. Among these are models for Parkinson’s disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, spinal cord injury models, a model for type 1diabetes induced by the combination of partial pancreatectomy and streptozotocin administration, and a hepatic fibrosis model induced by thioacetamide. The development of these models hasbeen supported by refinements in veterinary care, such as the careful design of anesthetic protocols and better understanding of pathogenic microorganisms. In the second part of this review,we present a compilation of practices currently in use at CIEA that provide optimal animal care and enable safe experimentation.

Common marmosets have attracted considerable attention as a small standard primate model in biomedical research. However, no marmoset diabetes model is available. Here, we established a marmoset diabetes model via the combination of partial pancreatectomy and intravenous streptozotocin (STZ). A partial pancreatectomy was performed in 11 common marmosets and multiple STZ doses were intravenously administered. Diabetes was diagnosed upon sustained hyperglycaemia (nonfasting blood glucose level >200 mg/dl). Blood glucose and biochemistry were periodically assessed, in addition to glucose tolerance testing, continual blood glucose determination using a continuous glucose monitoring system, urine testing and histological evaluation. In 8 of the 11 animals (73%), diabetes mellitus was induced. The diabetic marmosets also showed abnormal intravenous and oral glucose tolerance test results. Blood glucose levels decreased in response to human insulin administration. The hyperglycaemic state was irreversible and persisted for more than 3 months, and the animals’ condition was manageable via daily insulin administration. Thus, diabetes can be successfully induced and maintained in the common marmoset via partial pancreatectomy and STZ administration. This protocol effectively generates a valuable animal model for studying disease pathogenesis, risk factors and therapeutic interventions, including islet transplantation.

The common marmoset (Callithrix jacchus) is a New World Monkey that frequently serves as a model in biomedical research. Our knowledge of its anatomy is the fundament of the provision of the correct environment, housing, and care together with provision of accurate medical care in the case it gets wounded. In this anatomical research article, the focus is on the hand musculature, as it plays a pivotal role in the interaction with the environment and conspecifics. Surprisingly, anatomical works on the common marmoset are scarce. The available books and atlases are either outdated in terms of illustrations, providing only simplified line drawings, and/or fail to recapitulate the anatomy of the hand using contemporary anatomical nomenclature. The present work describes the myology of the hand, based on dissections of common marmoset cadavers. Color photographs taken during the subsequent steps of the examinations lead the reader through the textual descriptions. Dorsal and palmar views of the antebrachial muscles with influence on the wrist and hand as well as the intrinsic hand musculature are scrutinized. The findings are finally discussed in view of potential contradictions with the available literature. In addition, comparison is made with the rhesus monkey (Macaca mulatta) whose hand musculature was recently revisited. It is concluded that the hand musculature of both species is highly similar, although remarkable differences are present. This work could serve as an anatomical foundation for medical interventions of the injured hand.

Protocol for necropsy and tissue processing of the common marmoset, Callithrix jacchus, for histopathological analysis

The common marmoset (Callithrix jacchus) has attracted extensive attention for use as a non-human primate model in biomedical research, especially in the study of neuropsychiatric disorders. However, behavioral test methods are still limited in the field of marmoset research. The light-dark box is widely used for the evaluation of anxiety in rodents, but little is known about light-dark preference in marmosets. Here, we modified the light-dark test to study this behavior. The modified apparatus consisted of three compartments: one transparent open area and two closed opaque compartments. The closed compartments could be dark or light. We found that both adult and young marmosets liked to explore the open area, but the young animals showed more interest than adults. Furthermore, when one of the closed compartments was light and the other dark, the adult marmosets showed a preference for the dark compartment, but the young animals had no preference. These results suggest that the exploratory behavior and the light-dark preference in marmosets are age-dependent. Our study provides a new method to study exploration, anxiety, and fear in marmosets.

There has been recent increasing interest in the use of marmosets, a New World primate species, as a model in biomedical research. One of the principal advantages of marmosets as a research model is their rich vocal repertoire and communicative vocal behaviors displayed both in the wild and in captivity. Studies of this species' vocal communication system have the potential to reveal the evolutionary underpinnings of human speech, and therefore are of interest to the neuroscience and biology research communities. Here a recent research into the behavioral and neurobiological basis of marmoset vocal communication was reviewed and they argued for their broader value as a neuroscientific model. They discuss potential avenues for future research including developmental neurobiology and the application of modern molecular tools to the study of primate communication. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 286-299, 2017.

Development of stereotaxic recording system for awake marmosets (Callithrix jacchus)

RECEPTIVE FIELDS OF OPTIC TRACT AXONS AND LATERAL GENICULATE CELLS: PERIPHERAL EXTENT AND BARBITURATE SENSITIVITY.

Aping Science: A Critical Analysis of Research at the Yerkes Regional Primate Research Center Committee on Animal Models in Biomedical Research. Perspectives on Medical Research Volume 5 (1995). Medical Research Modernization Committee: New York. 102 pp. Paperback. Obtainable from the publishers, Box 2751 Grand Central Station, New York, NY 10163-2751, USA. Price US2 postage. - Volume 6 Issue 1

Zebrafish (Danio rerio) is an ideal model organism for the study of vertebrate development. This is due to the large clutches that each couple produces, with up to 200 embryos every 7 days, and to the fact that the embryos and larvae are small, transparent and undergo rapid external development. Using scientific literature research tools available online and the keywords Zebrafish, biomedical research, human disease, and drug screening, we reviewed original studies and reviews indexed in PubMed. In this review we summarized work conducted with this model for the advancement of our knowledge related to several human diseases. We also focused on the biomedical research being performed in Portugal with the zebrafish model. Powerful live imaging and genetic tools are currently available for zebrafish making it a valuable model in biomedical research. The combination of these properties with the optimization of automated systems for drug screening has transformed the zebrafish into "a top model" in biomedical research, drug discovery and toxicity testing. Furthermore, with the optimization of xenografts technology it will be possible to use zebrafish to aide in the choice of the best therapy for each patient. Zebrafish is an excellent model organism in biomedical research, drug development and in clinical therapy.

Squirrel monkeys have been a valuable animal model in biomedical research (Abee 2000). They have been utilized in a wide variety of study areas including, but not limited to, atherosclerosis, neuroscience, pharmacology, psychiatry, toxicology, and vision research. A quick search of on-line databases MEDLINE and PS YCHINFO indicates that approximately 200 articles have been published in the last 10 yr that have used behavioral testing of squirrel monkeys. Analysis of experimental manipulations of Saimiri behavior has been an important tool. Depending on the level of analysis needed, several different behavioral testing protocols have been used successfully in biomedical research using squirrel monkeys. If a predicted effect is on the whole organism, other than studying the natural behavior of an animal, investigating its interaction with social partners and its environment has been most appropriate. If the effects of interest are more limited, more specific tests of the squirrel monkey's motor performance, cognitive ability, or reflex actions may enable an investigator to isolate the consequence of the experimental intervention. The purpose of this article is to review how behavior has been employed using squirrel monkeys in biomedical research. We describe three general types of behavioral analysis: natural behavior, conditioned behavior, and neurobehavioral assessment profiles. Natural behavior refers to data collected on squirrel monkeys as they move about the environment. This type of analysis includes studies of animals in seminatural and captive laboratory environments as well as field studies. Although an investigator can arrange particular situations in all three study types, a key difference between behavioral analysis and conditioned tests is usually in the investigator's direct supply of rewards or punishments (conditions) in the latter. Conditioned behavior tests (cognitive, classical, and instrumental paradigms) are used to investigate the squirrel monkey's ability to learn or react to environmental stimuli. Classical conditioning entrains reflexive behavior to stimuli that do not normally elicit it. Cognitive and instrumental conditioning relies on animal tendencies to maximize rewards and minimize punishment in an effort to examine its

Nonhuman Primate Models in Biomedical Research

IntroductionThe gray mouse lemur (Microcebus murinus) is an important nonhuman primate model in biomedical research. Numerous studies investigated mouse lemur behavior and possible factors underlying interindividual variation in both, animal personality and cognitive performance. Some effects, such as an age‐related decline in executive functioning, have robustly been found across laboratory colonies; however, little is known about the brain structural substrates in mouse lemurs.MethodsHere, we provide first exploratory data linking in vivo magnetic resonance imaging of 34 mouse lemurs to performance in a standardized, touchscreen‐based task on object discrimination and reversal learning as well as to animal personality under different scenarios in an open field.ResultsHigh interindividual variability in both brain morphometric and behavioral measurements was found, but only few significant correlations between brain structure and behavior were revealed: Object discrimination learning was linked to the volume of the hippocampus and to temporal lobe thickness, while reversal learning was linked to thalamic volume and the thickness of the anterior cingulate lobe. Emergence latency into the open field correlated with volume of the amygdala. General exploration–avoidance in the empty open‐field arena correlated with thicknesses of the anterior cingulate lobe and fronto‐parietal substructures. Neophilia, assessed as exploration of a novel object placed in the arena, among others, related to the volume of the caudate nucleus.ConclusionIn summary, our data suggest a prominent role of temporal structures (including the hippocampus) for learning capability, as well as thalamic and anterior cingulate structures for cognitive flexibility and response inhibition. The amygdala, the anterior cingulate lobe, and the caudate nucleus are particularly linked to animal personality in the open‐field setting. These findings are congruent with the comparative psychological literature and provide a valuable basis for future studies elucidating aspects of behavioral variation in this nonhuman primate model.

BackgroundThe rhesus macaque (RM, Macaca mulatta) is the most important nonhuman primate model in biomedical research. We present the first genomic survey of wild RMs, sequencing 81 geo-referenced individuals of five subspecies from 17 locations in China, a large fraction of the species’ natural distribution.ResultsPopulations were structured into five genetic lineages on the mainland and Hainan Island, recapitulating current subspecies designations. These subspecies are estimated to have diverged 125.8 to 51.3 thousand years ago, but feature recent gene flow. Consistent with the expectation of a larger body size in colder climates and smaller body size in warmer climates (Bergman's rule), the northernmost RM lineage (M. m. tcheliensis), possessing the largest body size of all Chinese RMs, and the southernmost lineage (M. m. brevicaudus), with the smallest body size of all Chinese RMs, feature positively selected genes responsible for skeletal development. Further, two candidate selected genes (Fbp1, Fbp2) found in M. m. tcheliensis are involved in gluconeogenesis, potentially maintaining stable blood glucose levels during starvation when food resources are scarce in winter. The tropical subspecies M. m. brevicaudus showed positively selected genes related to cardiovascular function and response to temperature stimuli, potentially involved in tropical adaptation. We found 118 single-nucleotide polymorphisms matching human disease-causing variants with 82 being subspecies specific.ConclusionsThese data provide a resource for selection of RMs in biomedical experiments. The demographic history of Chinese RMs and their history of local adaption offer new insights into their evolution and provide valuable baseline information for biomedical investigation.

Connexins are gap junction components that are essential for acquiring normal hearing ability. Up to 50% of congenital, autosomal-recessive, non-syndromic deafness can be attributed to variants in GJB2, the gene that encodes connexin 26. Gene therapies modifying the expression of connexins are a feasible treatment option for some patients with genetic hearing losses. However, the expression patterns of these proteins in the human fetus are not fully understood due to ethical concerns. Recently, the common marmoset was used as a primate animal model for the human fetus. In this study, we examined the expression patterns of connexin 26 and connexin 30 in the developing cochlea of this primate. Primate-specific spatiotemporal expression changes were revealed, which suggest the existence of primate-specific control of connexin expression patterns and specific functions of these gap junction proteins. Moreover, our results indicate that treatments for connexin-related hearing loss established in rodent models may not be appropriate for human patients, underscoring the importance of testing these treatments in primate models before applying them in human clinical trials.