Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early Life Anxious Temperament

Abstract Background Children exhibiting extreme anxious temperament (AT) are at an increased risk to develop anxiety and depression. Our previous mechanistic and neuroimaging work in young rhesus monkeys links the central nucleus of the amygdala (Ce) 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 lateral Ce (CeL) neurons. 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, of which 14 were confirmed with high statistical confidence (FDR Conclusions These findings demonstrate that CeL PKCδ is associated with primate anxiety, provides evidence of a CeL to BSTLd 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.