Abstract
Background
Children exhibiting extreme anxious temperament (AT) are at an increased risk for
developing anxiety and depression. Our previous mechanistic and neuroimaging work
in young rhesus monkeys linked the central nucleus of the amygdala to AT and its underlying
neural circuit.
Methods
Here, we used laser capture microscopy and RNA sequencing in 47 young rhesus monkeys
to investigate AT’s molecular underpinnings by focusing on neurons from the lateral
division of the central nucleus of the amygdala (CeL). RNA sequencing identified numerous
AT-related CeL transcripts, and we used immunofluorescence (n = 3) and tract-tracing (n = 2) methods in a different sample of monkeys to examine the expression, distribution,
and projection pattern of neurons expressing one of these transcripts.
Results
We found 555 AT-related transcripts, 14 of which were confirmed with high statistical
confidence (false discovery rate < .10), including protein kinase C delta (PKCδ),
a CeL microcircuit cell marker implicated in rodent threat processing. We characterized
PKCδ neurons in the rhesus CeL, compared its distribution with that of the mouse,
and demonstrated that a subset of these neurons project to the laterodorsal bed nucleus
of the stria terminalis.
Conclusions
These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides
evidence of a CeL to laterodorsal bed nucleus of the stria terminalis circuit that
may be relevant to understanding human anxiety, and points to specific molecules within
this circuit that could serve as potential treatment targets for anxiety disorders.
Keywords
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Article info
Publication history
Published online: May 18, 2020
Accepted:
May 10,
2020
Received in revised form:
April 22,
2020
Received:
December 9,
2019
Identification
Copyright
© 2020 Society of Biological Psychiatry.
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- Central Amygdala Discovery Efforts in Primates Reveals New Clues on Anxious TemperamentBiological PsychiatryVol. 88Issue 8
- PreviewOur brains are built to consider and reflect on the unknown. These adaptive features protect us from potential threats in dynamic and complex environments, but they can also lead us to perseverate on perceived threats and fear an unknown future. Ranging across a spectrum from adaptive to maladaptive, anxious and fearful behavior exists in many animal species. In an effort to develop new therapeutics and understand the etiology of anxiety-related conditions, such as anxiety disorders, obsessive-compulsive disorder, panic disorder, and posttraumatic stress disorder, research using laboratory animal models has focused on the genetic, molecular, cellular, and brain systems contribution to anxiety and fear.
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