The amygdala, a sexually differentiated brain structure intimately involved in emotions, cognition, social behavior, and sexuality, is particularly important in monkeys for recognizing and responding to social context and danger. This structure continues to develop postnatally and is sexually differentiated prior to puberty, yet nothing is known about its contribution to sex differences in behavior and cognition, it impact on neuroendocrine function or its role in modulating social signals influencing puberty. Puberty in monkeys and humans is affected by social context and the amygdala may be one of the modulators of the interaction between social context and neuroendocrine function. We will investigate social, emotional, cognitive and neuroendocrine consequences of neonatal and post-pubertal amygdalectomy in male and female rhesus monkeys. Subjects will live in semi-natural complex social groups. A team with expertise in emotional regulation, cognition, neuroendocrine function, and social behavior, will track the development of these systems and relate changes in juvenile function to the pubertal transition and adult social behavior. Forty- eight monkeys, distributed between 8 male and 8 female controls, 8 neonatally amygdalectomized of each sex, and 8 post-pubertally lesioned subjects of each sex, will be created in two annual cohorts of 24. Neonatal gonadal function, anxiety, fear, and maternal attachment will be assessed along with extensive observations of social interactions in the subjects'natal group during the first year of life. Social observations, assessment of emotionality, and stress physiology will continue for the 2nd through 4th years of life. At two years of age, cognitive tasks, using continuously available computer kiosks, will assess object and spatial memory span and object discrimination. Sex differences in social interactions and social integration will be investigated through detailed observations of social behavior. At two years of age females will start intense endocrine sampling to assess pubertal timing as well as pubertal changes in social and sexual behavior. Three year old males will be removed from their natal group to simulate male migration and formed into bachelor groups for investigation of the pubertal transition. It is hypothesized that the different male and female natal social environments, combined with the sexually differentiated nature of amygdala function will result in different magnitudes of effect of amygdala damage, with males likely more severely affected than females. We hypothesize that amygdalectomized females will uniformly show early puberty. Altered amygdala function is found in a number of neurodevelopmental disorders and while amygdalectomy does not serve as a model for any single human mental disorder, understanding its functional effects on a range of behavioral, cognitive and neuroendocrine endpoints will be invaluable for understanding the developmental trajectory of alterations produced by early amygdala dysfunction in human neurodevelopmental disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH050268-15
Application #
8111666
Study Section
Neuroendocrinology, Neuroimmunology, and Behavior Study Section (NNB)
Program Officer
Simmons, Janine M
Project Start
1994-12-01
Project End
2013-07-31
Budget Start
2011-09-07
Budget End
2013-07-31
Support Year
15
Fiscal Year
2011
Total Cost
$499,434
Indirect Cost
Name
Emory University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Forger, Nancy G; Ruszkowski, Elara; Jacobs, Andrew et al. (2018) Effects of sex and prenatal androgen manipulations on Onuf's nucleus of rhesus macaques. Horm Behav 100:39-46
Stephens, Shannon B Z; Raper, Jessica; Bachevalier, Jocelyne et al. (2015) Neonatal amygdala lesions advance pubertal timing in female rhesus macaques. Psychoneuroendocrinology 51:307-17
Raper, Jessica; Stephens, Shannon B Z; Sanchez, Mar et al. (2014) Neonatal amygdala lesions alter mother-infant interactions in rhesus monkeys living in a species-typical social environment. Dev Psychobiol 56:1711-22
Goursaud, Anne-Pierre S; Wallen, Kim; Bachevalier, Jocelyne (2014) Mother recognition and preference after neonatal amygdala lesions in rhesus macaques (Macaca mulatta) raised in a semi-naturalistic environment. Dev Psychobiol 56:1723-34
Raper, Jessica; Stephens, Shannon B Z; Henry, Amy et al. (2014) Neonatal amygdala lesions lead to increased activity of brain CRF systems and hypothalamic-pituitary-adrenal axis of juvenile rhesus monkeys. J Neurosci 34:11452-60
Raper, Jessica; Bachevalier, Jocelyne; Wallen, Kim et al. (2013) Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys. Psychoneuroendocrinology 38:818-29
Stephens, Shannon B Z; Wallen, Kim (2013) Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates. Horm Behav 64:226-39
Raper, Jessica; Wallen, Kim; Sanchez, Mar M et al. (2013) Sex-dependent role of the amygdala in the development of emotional and neuroendocrine reactivity to threatening stimuli in infant and juvenile rhesus monkeys. Horm Behav 63:646-58
Raper, Jessica; Wilson, Mark; Sanchez, Mar et al. (2013) Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys. Psychoneuroendocrinology 38:1021-35
Wallen, Kim; Lloyd, Elisabeth A (2011) Female sexual arousal: genital anatomy and orgasm in intercourse. Horm Behav 59:780-92

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