Neonatal Amygdala Lesions in Rhesus Monkeys Living in a Semi-Naturalistic Environment: Effects on Emotional Behavior and Neuroendocrine Stress Response Öffentlichkeit
Raper, Jessica (2012)
Abstract
Abstract
The amygdala plays a critical role in the evaluation of salient and
threatening cues from the
environment and in the modulation of behavioral, autonomic, and
neuroendocrine responses to
threats. Much less know of is its potential role on the regulation
of the hypothalamic-pituitary-
adrenal (HPA) axis basal tone and on the development of emotional
and neuroendocrine
processes through the lifespan. The current study examined the
effects of neonatal amygdala
lesions in rhesus monkeys on basal and stress reactive HPA
function, as well as emotional
reactivity from birth to preadolescence. Neonatal amygdalectomy
spared the ability to express
emotional behaviors, but altered the modulation of those behaviors
based on the contextual
information provided by the salience of the threat. Interestingly,
the sex of the animal modulated
the behavioral effects of neonatal amygdala lesions, leading to
different patterns of emotional
behaviors depending on the sex and lesion status. Neonatal
amygdalectomized animals also had
elevated cortisol at 5 and 12 months of age, exaggerated cortisol
response to a stressor, and
increased corticotropin releasing factor (CRF) in cerebrospinal
fluid as compared to controls.
Pharmacological challenges used to investigate the neural
mechanisms of this exaggerated
glucocorticoid secretion revealed blunted response to a
corticotropin releasing hormone
challenge, suggesting a down-regulation of CRF receptors in the
anterior pituitary. Thus, the
amygdala plays a critical role in the development of both basal and
stress-related HPA axis
functions and in the expression of sexually dimorphic behaviors,
providing valuable insights into
the neural mechanism underlying the symptomatology of many
developmental neuropsychiatric
disorders.
Table of Contents
Table of Contents
General Introduction
.....................................................................................................................
11
Structure and Connectivity of the Amygdala
...........................................................................
11
Amygdala and Emotional Behavior
..........................................................................................
13
HPA axis Regulation
................................................................................................................
16
Amygdala and HPA axis interactions
.......................................................................................
18
Behavioral Development and Amygdala Maturation
...............................................................
20
Neonatal Lesions of the Amygdala and Emotional Behavior
................................................... 22
Neonatal Amygdala Lesions and HPA axis Regulation
...........................................................
25
Specific Aims
............................................................................................................................
27
HPA axis Basal Rhythm
........................................................................................................
27
Emotional Behavior
..............................................................................................................
27
HPA axis Reactive Stress Response
......................................................................................
28
HPA axis Functioning
...........................................................................................................
28
Manuscript I. Neonatal amygdala lesions alter basal cortisol levels
in infant rhesus monkeys. . 30
Abstract
.....................................................................................................................................
31
Introduction
...............................................................................................................................
32
Methods
....................................................................................................................................
35
Results
.......................................................................................................................................
44
Discussion
.................................................................................................................................
47
Acknowledgements
...................................................................................................................
53
Figure Captions
.........................................................................................................................
54
Figure 1. Representative cases of neonatal amygdala lesions.
............................................ 55
Figure 2. Basal cortisol levels.
.............................................................................................
56
Figure 3. Testosterone levels.
..............................................................................................
57
Table 1. Intended and unintended damage after neurotoxic lesions of
the amygdala ......... 58
Table 2. Surgical and Research Manipulation Factors
........................................................ 59
Manuscript II. Sex-dependent role of the amygdala in the
development of emotional reactivity to
threatening stimuli in infant rhesus monkeys.
..............................................................................
60
Abstract
.....................................................................................................................................
61
Introduction
...............................................................................................................................
62
Methods
....................................................................................................................................
64
Results
.......................................................................................................................................
70
Discussion
.................................................................................................................................
75
Acknowledgements
...................................................................................................................
83
Figure captions
..........................................................................................................................
84
Figure 1. Representative case of a neonatal amygdala lesion.
............................................. 86
Figure 2. Behavioral responses during the Human Intruder paradigm
in Infancy ............... 87
Figure 3. Behavioral responses toward the Novel Fruit Test
............................................... 88
Figure 4. Behavioral responses during the Human Intruder paradigm
in Preadolescence .. 89
Figure 5. Correlations between testosterone levels and yawning
........................................ 90
Table 1. Extent of damage after neurotoxic amygdala lesions
............................................ 91
Table 2. Behavioral ethogram
..............................................................................................
92
Table 3. Human intruder behavioral responses during infancy and
preadolescence ........... 93
Table 3. (continued)
..............................................................................................................
94
Manuscript III. Neonatal amygdala lesions alter normal functioning
of the hypothalamic-
pituitary-adrenal axis in juvenile rhesus monkeys
........................................................................
95
Abstract
.....................................................................................................................................
96
Introduction
...............................................................................................................................
97
Methods
..................................................................................................................................
100
Experiment 1
...........................................................................................................................
104
Results
.................................................................................................................................
107
Experiment 2
...........................................................................................................................
108
Results
.................................................................................................................................
112
Discussion
...............................................................................................................................
114
Acknowledgements
.................................................................................................................
123
Figure captions
........................................................................................................................
124
Figure 1. Cortisol and corticotropin releasing factor levels
............................................... 125
Figure 2. Response to neuropeptide pharmacological challenges
..................................... 126
Table 1. Intended and unintended damage after neurotoxic lesions of
the amygdala ....... 127
General Discussion
.....................................................................................................................
128
Is the amygdala important for the development of emotional behavior
expression? ............. 130
How does the present results inform on the role of the amygdala on
emotional reactivity in
neuropsychiatric disorders?
....................................................................................................
133
Is the amygdala important for normal functioning of the HPA-axis?
.................................... 135
How do these data inform on the role of the amygdala on HPA-axis
activity in
neuropsychiatric disorders?
....................................................................................................
143
Summary
.................................................................................................................................
145
Table 1. Summary of emotional reactivity results
.............................................................
147
Table 2. Summary of hormone results
...............................................................................
148
References
...................................................................................................................................
149
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