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genetic and
environmental determinants of primate
biobehavioral
development
Stephen J. Suomi, PhD, Head, Section on
Comparative Behavioral Genetics Kathlyn L. Robbins, PhD, Research
Psychologist Sue B. Higley, BA, Technician
Psychologist Courtney Shannon-Lindell, BA, Technician
Psychologist Peggy O’Neill Kimran Miller, PhD, Postdoctoral
Fellow Matthew F.X. Novak, PhD,
Postdoctoral Fellow Angela Ruggiero, BS, Postbaccalaureate
Fellow Katlyn Kerekes, BS, Technical
Training Fellow Halligan Lyons, BS, Technical
Training Fellow Lisa Morin, BS, Technical
Training Fellow Peter Roma, BS, Technical
Training Fellow Erica Sheldon, BS, Technical
Training Fellow Kenneth Vaughn, BS, Technical Training Fellow |
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Our
research involves broad-based investigation of primate biobehavioral development
through comparative longitudinal studies of rhesus monkeys and other nonhuman
primate species. Our primary research goals are to characterize distinctive
biobehavioral phenotypes in our rhesus monkey colony, to determine how
genetic and environmental factors interact to shape the monkeys’
development, and to assess the long-term biobehavioral consequences for
monkeys from different genetic backgrounds when they are reared in various
physical and social environments. A second major program of research
investigates how rhesus monkeys and other nonhuman primate species born and
raised under different laboratory conditions adapt to placement into
environments that model specific features of their natural habitat. Developmental
continuity of individual differences in rhesus monkey biobehavioral
development Higley S, Novak MF,
Ruggiero, Shannon-Lindell, Sheldon, Suomi, Vaughn Over
the past year, we developed a new experimental procedure to monitor rhesus
monkey maternal and fetal heart rate and blood pressure from the second
trimester of pregnancy to parturition; the procedure involves surgically
implanting indwelling catheters in both mother and fetus and recording data
online via a tethering device that does not impede the mother’s
locomotor or exploratory activity. The initial pregnancy subjected to testing
resulted in a successful birth and normal postnatal infant development.
Preliminary analyses of the prenatal data revealed patterns of maternal and
fetal heart rate and blood pressure changes that became increasingly
synchronous with approaching parturition. We are currently following
additional pregnancies. We also completed a study
evaluating the relative heritability of various components of our standard
neurobehavioral assessment battery for rhesus monkey infants throughout the
first 30 days of life. The analyses revealed significant heritability for the
Orientation, State Control, and Activity (but not Motor Maturity) clusters at
14 days of age. By 30 days, heritabilities had increased for the Orientation
and Motor Maturity clusters, remained stable for the State Control cluster,
and declined for the Activity cluster, suggesting marked changes in relative
heritabilities during the infants’ first month of life. We also
detected significant gender and early rearing condition components for three
of the four clusters, and these components tended to increase in relative
magnitude over the first month. A
collaborative study with NIAAA and NIMH researchers employed PET imaging
methodology to investigate possible differences in brain serotonin
transporter receptor distribution and affinity in rhesus monkey juveniles
that had been either reared by their biological mothers in small social
groups or nursery-reared with same-age peers during the first seven months of
life. Analyses of serotonin transporter ligand-binding potential and cerebral
blood flow revealed significant deficits in raphe, thalamus, striatum,
frontal, and parietal regions among peer-reared juveniles as compared with
their mother-reared counterparts, thereby demonstrating long-term effects of
variation in early rearing at the level of brain structure and function. Barr CS, Becker ML, Suomi SJ, Higley JD.
Relationship among CSF monoamine metabolite levels, alcohol sensitivity, and alcohol-related
aggression in rhesus macaques. Aggress
Behav 2003;29:288-301. Polymorphisms in gene
associated with serotonin metabolism Suomi; in
collaboration with Champoux, Higley J, Lesch, Newman Several
ongoing studies have focused on possible interactions between a polymorphism
(due to length variation in the promoter region) in 5-HTT, a candidate gene for impaired serotonergic function, and
differential early social experience. Over the past year, we published a
report of a specific gene-environment interaction in rhesus monkey
hypothalamic-pituitary-adrenal (HPA) axis responsiveness to short-term social
separation at seven months of age: monkeys with the “short” (LS)
allele exhibited excessive ACTH responsiveness relative to those with the
“long” (LL) allele, but only if they had been
nursery-peer–reared. In contrast, LS monkeys reared by their biological
mother did not differ in ACTH responsiveness from mother-reared LL subjects,
suggesting a “buffering” effect of maternal rearing. This
gene-environment interaction was significantly greater in female than in male
monkeys. We found a parallel pattern of gene-environment interaction
involving a polymorphism in the MAO
gene for levels of aggressive behavior exhibited by mother- and peer-reared
rhesus monkey juveniles. We are now in the process of determining whether
these and other specific polymorphisms are associated with specific
gene-environment interactions with respect to a variety of behavioral and
biological measures obtained throughout development in our rhesus monkey
population. As
a species, rhesus monkeys are notoriously aggressive compared with other
macaques (indeed, compared with most other primates). We were able to
genotype blood samples obtained from six other species of macaques ( Barr CS, Newman TK, Schwandt
M, Shannon C, Dvoskin RL, Lindell SG, Taubman J, Thompson B, Champoux M,
Lesch KP, Goldman D, Suomi SJ, Higley JD. Sexual dichotomy of an interaction
between early experience and the serotonin transporter gene promoter variant
in rhesus macaques. Proc Natl Acad Sci
USA 2004;101:12358-12363. Newman TK, Syagallo YV, Barr
CS, Wendland J, Champoux M, Graessie M, Suomi SJ, Higley JD, Lesch KP. MAOA
gene promoter variation and rearing experience influences aggressive behavior
in rhesus monkeys. Biol Psychiatry
2004, in press. Adaptation of
laboratory-reared monkeys to field environments Kerekes, Miller,
Morin, O’Neill Wagner, Roma, Shannon-Lindell, Suomi We assess adaptation by
examining behavioral repertoires and monitoring a variety of physiological
systems in monkeys throughout the lifespan, yielding broad-based indices of
relative physical and psychological well-being. In similar fashion, we assess
the responses of subjects to experimental manipulations of selected features
of their respective environments. Whenever possible, we collect field data
for appropriate comparisons. We also focus on investigating the cognitive,
behavioral, and social processes involved in adaptation to new settings and
circumstances. We began a pilot study to see
if rhesus monkey neonates were capable of “imitating” specific
facial expressions and hand movements directed toward them by a human
“model” in their first days of life. Such early imitative
capabilities have been reported for human neonates and are thought to be
reflexively mediated by “mirror” neurons, a recently
characterized class of visual-motor neurons found in Area F5 of the ventral
premotor cortex. Preliminary findings indicated that some (but not all)
rhesus monkey newborns were able to mimic specific facial expressions
involving differential mouth and tongue movements, but not until their second
or third day of life. Interestingly, the infants that demonstrated this
imitative capacity spent significantly more time visually focusing on facial
stimuli on Day 1 than those that did not exhibit any imitative behaviors on
subsequent days. We are now testing additional infants and carrying out
follow-up behavioral observations and biological sampling of the original
infants to determine if individual differences in early imitative
capabilities predict individual differences in biobehavioral functioning
throughout subsequent development. We also completed most of the
analyses of behavioral and biological data collected in a study in which some
nursery-reared rhesus monkey infants (“masters”) were given
operant control over access to highly desirable food treats, whereas other
nursery-reared infants (“yoked controls”) received the same
treats in the absence of any control. Analyses of behavioral and
neuroendocrine data collected both in the infants’ home cages and in a
novel environment indicated that the “master” subjects engaged in
more exploratory and less anxious-like behavior and had lower levels of HPA
activity than their yoked control counterparts. We are currently analyzing
CSF monoamine metabolite concentrations obtained throughout the study. We completed data collection
for a long-term prospective longitudinal study of maternal behavior across
three successive generations of rhesus monkey females born and raised in our
five-acre outdoor field enclosure. Analyses of the data should enable us to
determine the degree to which specific patterns of maternal behavior exhibited
toward successive offspring resemble those exhibited by the females’
mothers and grandmothers in both previous and (for those older females who
continue to produce and rear offspring) concurrent years in each year’s
birth cohort. Analyses of immunological data collected in another long-term
prospective longitudinal study of free-ranging rhesus monkeys residing on the
island of Cayo Santiago in Puerto Rico during the annual trapping of monkeys
(for veterinary examinations) revealed a significant relationship between
measures of immune system and HPA axis functioning and maternal dominance
status in juvenile subjects. Monkeys whose mothers were low-ranking within
their natal social groups exhibited higher cytotoxicity, greater numbers of
C8 and C16 Raij targets, and higher concentrations of plasma cortisol than
the offspring of more dominant mothers, demonstrating that differences in
maternal rank have significant consequences not only for offspring social and
emotional development but also for immune system and adrenocortical
functioning. Another study investigated the
relationship between social dominance ranking and food consumption as a
function of food novelty and relative accessibility in a group of tufted
capuchin monkeys. High-ranking group members consumed significantly more food
that was easily accessible than portions hidden from view, whereas the
reverse held for low-ranking subjects. Rates of aggressive threats by
high-ranking monkeys toward lower-ranking monkeys were inversely related to
the amount of food consumed by low-ranking group members. Thus, although
tufted capuchin monkeys have been described as a relatively peaceable species
(at least compared with rhesus monkeys) and readily share food in a variety
of naturalistic and captive situations, dominance-related differences in food
consumption appear to be mediated by differences in the relative occurrence
and direction of threat behavior. Barr CS, Newman TK, Becker
ML, Parker CC, Champoux M, Lesch KP, Suomi SJ, Goldman D, Higley JD. The
utility of the non-human primate: model for studying gene by environment
interactions in behavioral research. Genes
Brain Behav 2003;2:336-340. Novak MF. Fetal-maternal
interactions: psychobiological precursors to adaptive infant development. Curr Top Dev Biol 2004;59:37-60. Suomi SJ. Gene-environment
interactions and the neurobiology of social conflict. Ann NY Acad Sci 2004;1008:132-139. Suomi SJ. How
gene-environment interactions can influence emotional development in rhesus
monkeys. In: Garcia-Cole C, Bearer EL, Lerner RM, eds. Nature and Nurture: the Complex Interplay of Genetic and
Environmental Influences on Human Development. Suomi SJ. How
gene-environment interactions shape biobehavioral development: lessons from
studies with rhesus monkeys. Res Human
Dev 2004;1:205-222. Tool use in rhesus
monkeys Suomi; in
collaboration with Novak MA, Westergaard We assessed tool-using
capabilities in juvenile rhesus monkeys for tasks routinely solved by most
capuchin monkeys. Subjects were required to use a rake to retrieve a reward
located outside the cage or to use a PVC pipe to remove a reward from a tube.
The sample of eight rhesus monkeys subjected to testing exhibited strong
individual differences in capability. Two monkeys quickly solved the
tool-using tasks, and three monkeys eventually solved them. Two monkeys
showed partial understanding of the tasks but could not reliably obtain a
reward, and the eighth rhesus subject failed both tasks. Successful tool
users showed persistence in the tasks and varied their responses. Pivotal to
their success was learning to push a tool away from them rather than pull it
toward them. Unsuccessful monkeys became fixated on nonproductive strategies.
Westergaard GC, Liv C, Rocca
AM, Cleveland A, Suomi SJ. Tufted capuchins (Cebus apella) attribute value to
food and tools during voluntary exchanges with humans. Anim Cogn 2004;7:19-24. COLLABORATORS Christina Barr,
PhD, DVM, Laboratory of Clinical
Sciences, NIAAA, Michelle Becker,
PhD, Laboratory of Clinical Sciences,
NIAAA, Allyson J.
Bennett, PhD, Aron D. Brascomb,
PhD, Gayle D. Byrne,
PhD, Maribeth Champoux,
PhD, Center for Scientific Review,
DCPS, Carlo Contoreggi, MD, Brain Imaging
Branch, NIDA, Baltimore, MD Barbara DeVinney,
PhD, Office of Behavioral and Social
Science Research, OD, Pier Ferrari, PhD,
Phillip W. Gold,
MD, Clinical Neuroendocrinology Branch,
NIMH, David A. Goldman,
MD, Laboratory of Neurogenetics, NIAAA,
J.D. Higley, PhD, Laboratory of Clinical Studies, NIAAA, Masanori Ichise,
PhD, Molecular Imaging Branch, NIMH, Robert Innis, MD, Molecular Imaging Branch, NIMH, Mark L.
Laudenslager, PhD, K. Peter Lesch,
MD, Timothy K. Newman,
PhD, Laboratory of Clinical Sciences,
NIAAA, Melinda A. Novak,
PhD, Eric Phoebus, PhD,
Becky Raboy, PhD, Melanie L.
Schwandt, PhD, Laboratory of Clinical
Studies, NIAAA, Susan E. Shoaf,
PhD, Laboratory of Clinical Studies,
NIAAA, Angelika Timme, PhD, Freie
Universität Berlin, Germany Elisabetta Visalberghi, PhD, Istituto
de Scienze e Technologie della Cognizione, CNR, Rome, Italy Gregory C.
Westergaard, PhD, Alpha Genesis, Inc., For further information, contact suomis@mail.nih.gov |