Leonard A. Rosenblum

Handbook of squirrel monkey research

1 The Taxonomy and Distribution of Squirrel Monkeys (Saimiri).- 1. Introduction.- 2. Methodology.- 3. Methods.- 4. Results.- 4.1. Saimiri sciureus sciureus.- 4.2. Saimiri sciureus boliviensis.- 4.3. Saimiri sciureus cassiquiarensis.- 4.4. Saimiri sciureus oerstedii.- 4.5. Saimiri madeirae.- 5. Discussion.- Appendix 1. Taxonomic Borborygme.- Appendix 2. Specimens Examined.- References.- 2 The Behavior of Squirrel Monkeys (Saimiri) in Natural Environments.- 1. Introduction.- 2. Specializations.- 2.1. Diet.- 2.2. Locomotion.- 2.3. Habitat.- 3. Activity Pattern.- 4. Group Size.- 5. Home Range.- 6. Social Behavior and Organization.- 6.1. Mating Activities.- 6.2. Birth Season.- 6.3. After Birth Season.- 6.4. Juveniles.- 6.5. Sexual Maturation.- 6.6. Communication.- 7. Relations with Other Species.- References.- 3 Cognition in Squirrel Monkeys: A Contemporary Perspective.- 1. Introduction.- 2. Sensory, Motor, and Cognitive Attributes Underlying Behavior.- 2.1. Vision and Looking Behavior.- 2.2. Attention.- 2.3. Habituation and Sensitization.- 2.4. Memory.- 2.5. Response to Novelty (Curiosity).- 2.6. Tempo of Motor Activity.- 2.7. Vigor and Frequency of Motor Activity.- 2.8. Variability of Motor Activity.- 2.9. A Heuristic Approach to Interspecific Comparisons of Cognitive and Sensorimotor Attributes.- 3. Performance on Selected Laboratory Tasks.- 3.1. Discrimination and Discrimination-Reversal.- 3.2. Concept Learning.- 3.3. Problem-Solving.- 4. Expression of Cognitive and Sensorimotor Characteristics in Everyday Behavior.- 4.1. Use of Space.- 4.2. Feeding and Activity Patterns.- 4.3. Group Cohesion and Dispersion.- 5. Topics for Future Research.- 6. Conclusion.- References.- 4 Squirrel Monkey Communication.- 1. Introduction.- 2. Overview of the Vocal Repertoire.- 2.1. Previous Studies of the Squirrel Monkey Vocal Repertoire.- 2.2. Major Functional Classes of Vocalizations.- 2.3. Infant Vocalizations.- 3. Inherited and Experiential Influences on Squirrel Monkey Vocalization.- 3.1. Introduction.- 3.2. Inherited Characteristics of the Squirrel Monkey Isolation Call.- 4. Visual Displays.- 4.1. Introduction.- 4.2. Facial Expressions.- 5. Olfactory Communication.- 6. Conclusion.- References.- 5 Physiological Consequences of Maternal Separation and Loss in the Squirrel Monkey.- 1. Introduction.- 2. Normal Development and Basic Separation Procedures.- 3. Adrenal Responses to Maternal Separation.- 4. Effect of Environmental Conditions and Social Support.- 5. Effect of Repeated Separation Experiences.- 6. Importance of Adrenal Activation during Separation.- 7. Effect of Separation on the Immune System.- 8. Neurotransmitter Activity during Separation.- 9. General Considerations.- References.- 6 Effects of Surrogate-Rearing on the Infant Squirrel Monkey.- 1. Introduction.- 2. Responsiveness to the Surrogate.- 3. Responses to Separation and Novelty.- 4. Social Behavior.- 5. Atypical Behaviors.- 6. Summary of Comparisons with Macaques.- References.- 7 Reproductive Cyclicity and Breeding in the Squirrel Monkey.- 1. Introduction.- 2. The Reproductive Cycle.- 2.1. Cycle Length.- 2.2. Cycle Endocrinology.- 2.3. Seasonal Influences and Captivity Adaptation.- 3. Ovulation and Fertilization.- 3.1. Normal Follicular Morphology.- 3.2. Ovulation Induction.- 3.3. Fertilization.- 4. Captivity Breeding and Artificial Insemination.- 5. Pregnancy.- 5.1. Diagnosis.- 5.2. Gestation Length.- 5.3. Time of Implantation.- 5.4. Placental Physiology.- 5.5. Stillbirth and Abortion.- 6. Embryonic Development.- 7. Pregnancy Outcome.- 8. Summary.- References.- 8 The Endocrine System of the Squirrel Monkey.- 1. Introduction.- 2. Hormone Profile.- 3. Annual Reproductive Pattern.- 4. Diurnal Hormone Rhythm.- 5. Hormone Changes at Puberty.- 6. Effect of Body Weight.- 7. Hormone Differences in Saimiri Females.- 8. Psychological Influences on Hormone Secretion.- 9. General Considerations.- References.- 9 Thermoregulation in the Squirrel Monkey.- 1. Basic Concepts.- 2. Autonomic Thermoregulatory Responses.- 2.1. Method of Partitional Calorimetry.- 2.2. Stitt and Hardys Experiment.- 2.3. Basic Data on Autonomic Thermoregulation.- 2.4. Probing Autonomic Capabilities with Thermodes.- 2.5. Autonomic Thermoregulation during Fever.- 2.6. Effects of CNS Lesions and Chemical Agents Other Than Pyrogens.- 2.7. Circadian Variations in Body Temperature.- 2.8. Autonomic Thermoregulation during Exposure to Microwave Fields.- 3. Behavioral Thermoregulation.- 3.1. Natural (Instinctive) Thermoregulatory Behaviors.- 3.2. Operant Control of the Thermal Environment.- 3.3. Probing Changes in Thermoregulatory Behavior with Thermodes.- 3.4. Important Parameters of Central Thermal Stimulation.- 3.5. Interaction between Behavioral and Autonomic Thermoregulatory Responses.- References.- 10 Sneezing Behavior in the Squirrel Monkey and Its Biological Significance.- 1. Introduction.- 2. Sneezing Behaviors: A Closer Look.- 3. On Functions and Effects.- 4. Sneezing Behaviors: What Function?.- 5. The Hypotheses on Trial.- 6. Sneezing: Functional Aspects.- 7. Epilogue.- References.- 11 Visual System of the Squirrel Monkey.- 1. Introduction.- 2. Organization of the Visual System.- 2.1. The Eye.- 2.2. Subcortical Visual Centers.- 2.3. Visual Cortex.- 3. Visual Capacities.- 3.1. Some Practical Issues.- 3.2. Visual Sensitivity.- 3.3. Color Vision.- 3.4. Spatial Vision.- 3.5. Binocular Vision.- References.- 12 Use of Squirrel Monkeys in Cardiovascular Research.- 1. Introduction.- 2. Naturally Occurring Atherosclerosis.- 2.1. Early Reports.- 2.2. Leticia, Colombia Study 1967.- 2.3. Squirrel Monkeys Compared to Other New World Monkeys.- 2.4. Histological Characteristics.- 3. Dietary Effects on Atherosclerosis.- 3.1. Summary of Lipid Changes.- 3.2. Composition of Diet.- 3.3. Type of Dietary Fat.- 3.4. Genetic Influences on Diet-Induced Atherosclerosis.- 4. Additional Effects on Diet-Induced Atherosclerosis.- 4.1. Effects of Age and Sex.- 4.2. Effects of Hypothyroidism, Insulin Deficiency, and Renally Induced Hypertension.- 4.3. Effects of Psychic Stress.- 5. Summary of Lesions and Complications of Atherosclerosis.- 5.1. Summary of Lesions by Location.- 5.2. Congestive Heart Failure.- 5.3. Myocardial Infarction.- 5.4. Aneurysms.- 5.5. Regression of Diet-Induced Atherosclerosis.- 6. Stress-Induced Cardiomyopathy.- 7. Behaviorally Induced Hypertension.- 8. Diseases Complicating the Use of Squirrel Monkeys in Cardiovascular Research.- 8.1. Cholelithiasis.- 8.2. Glomerulonephritis.- 8.3. Aortitis.- 8.4. Trypanosomiasis.- 9. Conclusion.- References.- 13 Behavioral Pharmacology of the Squirrel Monkey.- 1. Introduction: Procedures in Behavioral Pharmacology.- 1.1. Behavioral Pharmacology.- 1.2. Schedule-Controlled Behavior.- 1.3. Schedules Using Behavior Maintained by Food Presentation or Drug Injection.- 1.4. Schedules Using Noxious Stimuli.- 2. Determinants of the Behavioral Effects of Drugs.- 2.1. Response Rate.- 2.2. Behavioral and Pharmacological History.- 2.3. Nature of the Maintaining Event.- 2.4. Environmental Context.- 3. Behavioral Effects of Drugs in the Squirrel Monkey.- 3.1. Psychomotor Stimulants.- 3.2. Antianxiety Drugs, Sedative-Hypnotics, and Serotonin Antagonists.- 3.3. Antipsychotic Drugs.- 3.4. Opiates and Opiate Antagonists.- 3.5. Miscellaneous Compounds.- 4. Discriminative Stimulus Properties of Drugs.- 5. Drugs As Consequent Events.- 6. Drug Effects on Social Behavior.- 7. Comparison of Behavioral Effects of Drugs in the Squirrel Monkey with Other Species.- 8. Summary and Conclusions.- References.- 14 Nutrition and Metabolism of the Squirrel Monkey.- 1. Diet.- 1.1. Natural Habitat Diets.- 1.2. Diets Fed to Captive Animals.- 2. Requirements for Specific Nutrients.- 2.1. Introduction.- 2.2. Calorie Requirements.- 2.3. Protein Requirements.- 2.4. Fat Requirements.- 2.5. Carbohydrate Requirements.- 2.6. Mineral Requirements.- 2.7. Vitamin Requirements.- 2.8. Fiber.- 3. Growth and Body Composition As Affected by Diet.- 3.1. Infants.- 3.2. Adults.- 4. Nutritional and Metabolic Interactions.- 4.1. Introduction.- 4.2. Carbohydrate Metabolism: Glucose Tolerance.- 4.3. Protein Metabolism and PCM.- 4.4. Lipid and Lipoprotein Metabolism.- References.- 15 Immunology and Pathology of the Squirrel Monkey.- 1. Introduction.- 2. Simian Immunology.- 3. Agents of Disease.- 4. Infectious Agents, Immunological and Pathological Responses.- 4.1. Bacterial Infections.- 4.2. Fungal Infections.- 4.3. Parasitic Infections.- 4.4. Viral Infections.- 5. Comments and Perspectives.- References.- 16 Medical Care and Management of the Squirrel Monkey.- 1. Introduction.- 2. Colony Husbandry.- 2.1. Housing and Cage Requirements.- 2.2. Colony Records.- 3. Principles of Medical Management.- 3.1. Preventive Medicine.- 3.2. Therapeutic Approaches and Restraint.- 3.3. Methods of Treatment.- 4. Diseases of the Squirrel Monkey.- 4.1. Bacterial Diseases.- 4.2. Viral Infections.- 4.3. Parasitic Diseases.- 4.4. Deficiency Diseases.- 4.5. Other Diseases.- 5. Normative Data.- References.

Variable foraging demand rearing: sustained elevations in cisternal cerebrospinal fluid corticotropin-releasing factor concentrations in adult primates

BACKGROUND The authors previously reported elevated cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations in juvenile primates nursed by mothers undergoing experimentally imposed unpredictable foraging conditions in comparison to normally reared controls. The purpose of the present study was to determine if these changes would endure into young adulthood. METHODS Cisternal CSF samples were obtained from those unpredictably reared young adult primates who had been previously studied as juveniles and age-matched ad libitum normally reared controls. Samples were assayed for CSF CRF. RESULTS Concentrations of CSF CRF were significantly elevated in the unpredictably reared sample in comparison to the ad libitum-reared control group. A significant positive correlation was noted between juvenile and young adult CSF CRF values within the unpredictably reared cohort. CONCLUSIONS Disturbances of maternal-infant attachment processes have an enduring impact on primate CRF function into young adulthood. The CRF elevations following unpredictable maternal foraging conditions appear traitlike in nature.

Early-Life Stress and the Development of Obesity and Insulin Resistance in Juvenile Bonnet Macaques

Stress is a risk factor for chronic illnesses such as obesity, type 2 diabetes, and hypertension and has been postulated to cause the metabolic syndrome via perturbation of the hypothalamo-pituitary-adrenal (HPA) axis. In our model of early-life stress (variable foraging demand [VFD]), food insecurity is imposed on monkey mothers for 16 weeks beginning when their nursing offspring are 3–5 months of age. Under VFD, food availability is never restricted, and the infants growth is unaffected. VFD rearing does, however, cause a range of neurobiological abnormalities, including dysregulation of the HPA axis, manifested in abnormal cerebrospinal fluid cortisol and corticotropin-releasing factor levels. We previously reported spontaneous occurrence of metabolic syndrome in 14% of normally reared peripubertal bonnet macaques given ad libitum access to standard monkey chow. Here, we show that compared with normally reared monkeys, peripubertal VFD juveniles exhibit greater weight, BMI, abdominal circumference, and glucagon-like peptide-1 and decreased glucose disposal rates during hyperinsulinemic-euglycemic clamps. Our data suggest that early-life stress during a critical period of neuro development can result in the peripubertal emergence of obesity and insulin resistance.

EFFECTS OF SEPARATION FROM MOTHER ON THE EMOTIONAL BEHAVIOR OF INFANT MONKEYS

After studying emotion for more than 30 years, P. T. Young wrote, “A developmental view of the organism is ordinarily needed to recognize and name emotions consistently.” (Young, 1961, p. 41 1 ) . In our laboratory we have studied emotional behavior within a developmental context, first by noting its speciestypical ontogeny under relatively undisturbed conditions, and then by studying the reactions of young infants when they were bereft of their mothers by our design. For six years we have been studying numerous groups of two species of macaque, pigtails (Macaca nernestrina) and bonnets (Macaca radiata) . Each group consists of a wild-born adult male, four or five wild-born adult females, and their laboratory-born offspring. To date, more than 60 infants have been born, of whom 57 are living. Some mothers have had four or five offspring, with whom they still live together in their original groups. During systematic observations (Kaufman & Rosenblum, 1966) of the various groups, we were impressed by a marked difference between these closely related species in their tendency toward physical closeness with neighbors (Rosenblum et al., 1964). In bonnet groups, adult members spend many hours in close passive contact with each other, often in huddles (FIGURE 1 ) , whereas pigtail adults usually do not make physical contact (FIGURE 2) except to engage in a more dynamic social interaction such as mating, grooming, or fighting. This species difference appeared rapidly when groups were first formed, and was not altered appreciably by food deprivation (Rosenblum et al., in press) or by systematic changes in the ambient temperature between 72’ and 8 8 O F. More relevant to this paper is the fact that bonnet females remain in close physical contact with each other even after the birth of infants (FIGURE 3 ) , whereas pigtail mothers with infants tend to remain apart from other females (FIGURE 4 ) . This consistent and statistically significant difference in spatial propinquity between the species appears to reflect a significant character of the basic structure of their social behavior, as it may be seen in the behavior of the mother-infant dyad and the development of the young (Rosenblum & Kaufman, 1967; Kaufman & Rosenblum, in press a) . Bonnet mothers are more relaxed about their infants than pigtail mothers: they permit them more interaction with others; they guard, restrain, and retrieve the infants less (FIGURE 5); they wean less; and they punish less (FIGURE 6). Bonnet infants, accordingly, show differences from pigtails in their development that seem to include emotional differences. They appear to be more secure: they are less dependent on their mothers in that they go away from them more often, for further distances, and for longer periods; they are freer to approach other members of the group, both adults and peers; and they spend more time in social play, whereas pigtail infants spend more time in isolated play, although the total amount of play is similar in the two species. We may see here a mechanism of great importance in the perpetuation of the species-characteristic difference in spatial patterning and temperament.

Symbiosis in parent-offspring interactions

1. A Conceptual Framework for the Study of Parent-Young Symbiosis.- 2. Reciprocity and Resource Exchange: A Symbiotic Model of Parent-Offspring Relations.- 3. The Coordinate Roles of Mother and Young in Establishing and Maintaining Pheromonal Symbiosis in the Rat.- 4. The Mother-Infant Interaction as a Regulator of Infant Physiology and Behavior.- 5. Physiological Mechanisms Governing the Transfer of Milk from Mother to Young.- 6. The Thermoenergetics of Communication and Social Interactions among Mongolian Gerbils.- 7. Biparental Care: Hormonal and Nonhormonal Control Mechanisms.- 8. Assessing Caregiver Sensitivity to Infants: Toward a Multidimensional Approach.- 9. Psychoendocrine Responses of Mother and Infant Monkeys to Disturbance and Separation.- 10. Allometric Influences on Primate Mothers and Infants.- 11. Costs and Benefits of Mammalian Reproduction.

A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors

BACKGROUND Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. METHODS Bonnet macaque (Macaca radiata) mother-infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). RESULTS In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate-glutamine-gamma-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated (r = -.638, p =.014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. CONCLUSIONS These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates

Male bonnet monkeys (Macaca radiata) were subjected to the variable foraging demand (VFD) early stress paradigm as infants, MRI scans were completed an average of 4 years later, and behavioral assessments of anxiety and ex-vivo corpus callosum (CC) measurements were made when animals were fully matured. VFD rearing was associated with smaller CC size, CC measurements were found to correlate with fearful behavior in adulthood, and ex-vivo CC assessments showed high consistency with earlier MRI measures. Region of interest (ROI) hippocampus and whole brain voxel-based morphometry assessments were also completed and VFD rearing was associated with reduced hippocampus and inferior and middle temporal gyri volumes. The animals were also characterized according to serotonin transporter genotype (5-HTTLPR), and the effect of genotype on imaging parameters was explored. The current findings highlight the importance of future research to better understand the effects of stress on brain development in multiple regions, including the corpus callosum, hippocampus, and other regions involved in emotion processing. Nonhuman primates provide a powerful model to unravel the mechanisms by which early stress and genetic makeup interact to produce long-term changes in brain development, stress reactivity, and risk for psychiatric disorders.

Differing concentrations of corticotropin-releasing factor and oxytocin in the cerebrospinal fluid of bonnet and pigtail macaques

The two neuropeptides corticotropin-releasing-factor (CRF) and oxytocin (OT) may produce opposing behavioral effects - elevations of the former have been associated with anxiety and social vigilance and reductions of the latter with reduced social affiliation. We sought to test the hypothesis that, within the primate macaque genus, the more gregarious, affiliative, and affectively stable bonnet species (Macaca radiata) would exhibit lower cerebrospinal fluid (CSF) CRF and higher CSF OT concentrations in comparison to its close relative, the temperamentally volatile and socially distant pigtail (Macaca nemestrina). Cisternal CSF samples were obtained from young adult male and female pigtail and bonnet macaques, and CRF and OT concentrations were measured by radioimmunoassay. Pigtail macaques exhibited significantly higher concentrations of CSF CRF and significant lower concentrations of CSF OT than bonnet macaques. Results were not attributable to age or sex differences in group composition. When included together in a multiple regression, CRF and OT showed a multiple R of 0.76, accounting for more than half of the species variance. Although species differences in the bioeffectiveness of these peptides may possibly confound the observed biobehavioral relationships, in the absence of any existing data to that effect, the current findings appear in accordance with the hypothesis and consistent with previously reported species-typical behaviors observed in these macaques.

Annual reproductive strategy of the squirrel monkey (Saimiri sciureus).

The physiological and behavioral factors underlying the annual reproductive cycle of the squirrel monkey were evaluated under controlled laboratory conditions. Mating activity following the formation of two social groups served to synchronize the reproductive phases during the subsequent year of observation. Changes in male and female reproductive status were assessed during four designated phases: breeding, pregnancy, lactation and fatting. Behavioral and somatic changes in gonadectomized subjects, living in the social groups, were also evaluated. The variations in behavior and physiology across the year were considered in terms of factors constraining the timing of the natural reproductive pattern.

Correlations between Hippocampal Neurogenesis and Metabolic Indices in Adult Nonhuman Primates

Increased neurogenesis in feeding centers of the murine hypothalamus is associated with weight loss in diet-induced obese rodents (Kokoeva et al., 2005 and Matrisciano et al., 2010), but this relationship has not been examined in other species. Postmortem hippocampal neurogenesis rates and premortem metabolic parameters were statistically analyzed in 8 chow-fed colony-reared adult bonnet macaques. Dentate gyrus neurogenesis, reflected by the immature neuronal marker, doublecortin (DCX), and expression of the antiapoptotic gene factor, B-cell lymphoma 2 (BCL-2), but not the precursor proliferation mitotic marker, Ki67, was inversely correlated with body weight and crown-rump length. DCX and BCL-2 each correlated positively with blood glucose level and lipid ratio (total cholesterol/high-density lipoprotein). This study demonstrates that markers of dentate gyrus neuroplasticity correlate with metabolic parameters in primates.