Fear Learning, Conditioned Inhibition, and Extinction In Adult Macaques Open Access

Kazama, Andrew Masami (2010)

Permanent URL: https://etd.library.emory.edu/concern/etds/qj72p7584?locale=en
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Abstract


Abstract
Fear Learning, Conditioned Inhibition, and Extinction
In Adult Macaques
By Andy M. Kazama
Our current understanding of the neural circuitry of fear responses supports an
amygdalocentric model, in which the amygdala is critical for fear learning but the
magnitude of fear responses can be down-regulated by either the hippocampus or the
orbital frontal cortex when safety signals are detected. However, since much of this
evidence comes either from correlative human neuroimaging studies and clinical
populations suffering from non-selective brain damage, or from experimental studies in
rodents that may not possess prefrontal regions homologous to those found in primates, it
still is unclear whether these regulatory mechanisms are critical for safety signal learning.
To this end, we tested 24 adult rhesus macaques that had received either neonatal sham-
operations or neonatal amygdala, orbital frontal cortex, or hippocampal lesions in the first
few days of in life (N = 6 in each group) in a fear-potentiated startle paradigm developed
in rodents and humans (AX+/BX-). As predicted, neonatal damage to the amygdala retarded

fear learning but had no effect on safety signal learning, the modulation of fear, or extinction.

However, neonatal damage to areas 11
and 13 of the orbital frontal cortex had no effects on any phase of the paradigm,
suggesting that areas outside the middle orbital frontal cortex regions may be critical for
down-regulating the amygdala during emotion regulation. Similarly, four of the six
animals with early hippocampal damage had no difficulty in fear/safety signal learning,
modulation or extinction. However, two animals with early hippocampal damage were
severely impaired in their ability to learn either the fear or safety signals. The results
seen in early hippocampal damage appear to be related to sparing both in emotion
regulation as well as contextual learning and memory, thus it remains to be seen whether
or not damage received late in life would affect fear/safety signal learning.

Table of Contents


Table of Contents
General Introduction……………………………………………………………………1

The Amygdalocentric Model of Emotion Regulation…..…………………………….2

Human Studies………………………………………………………………………...3

Rodent Models……………….………………………………………………………..7

Non-Human Primate Models.………….…………………………………………….10

Specific Hypotheses…………………………………………………………………12
Manuscript I: Effects of Neonatal Amygdala Lesions………………………………..14
Abstract………..…………………………….…………………….......….………….15
Introduction......……………………………………………………………………….17
Methods…..………………………...…………………………………….…………...19
Results………………………………………………………………………………...27
Discussion……..……………………………………………………………………...30
Manuscript II: Effects of Neonatal Lesions of OFC Areas 11 & 13………………...49
Abstract………..……………………………….……………………………………..50
Introduction………………………………………………………………………......51
Methods…..…………………………………………………………………………..53
Results………………………………………………………………………………..61
Discussion……..……………………………………………………………………..64
Manuscript III: Effects of Neonatal Hippocampal Lesions………………………....80
Abstract………..……………………………………………………………………..81
Introduction…………………………………………………………………………..82
Methods…..…………………………………………………………………………..84
Results………………………………………………………………………………..91

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