1. Transcriptional Profiling of Primate Central Nucleus of the Amygdala Neurons to Understand the Molecular Underpinnings of Early-Life Anxious Temperament
- Author
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Andrew S. Fox, Tade Souaiaia, Rothem Kovner, Marissa K. Riedel, Ned H. Kalin, Jonathan A. Oler, Julie L. Fudge, Patrick H. Roseboom, Delores A. French, James A. Knowles, Cooper. E. Goss, and Eva M. Fekete
- Subjects
0301 basic medicine ,media_common.quotation_subject ,Microcircuitry ,Anxiety ,Stress ,Medical and Health Sciences ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neuroimaging ,Protein kinase C delta ,biology.animal ,medicine ,Animals ,Primate ,Temperament ,Bed nucleus of the stria terminalis ,Biological Psychiatry ,Protein kinase C ,030304 developmental biology ,media_common ,Neurons ,Psychiatry ,0303 health sciences ,biology ,Central nucleus of the amygdala ,Central Amygdaloid Nucleus ,Psychology and Cognitive Sciences ,Retrograde tracing ,RNA ,Fear ,Biological Sciences ,Macaca mulatta ,Stria terminalis ,030104 developmental biology ,medicine.anatomical_structure ,medicine.symptom ,Somatostatin ,Nucleus ,Neuroscience ,030217 neurology & neurosurgery - Abstract
BackgroundChildren 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.MethodsHere, 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.ResultsWe 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.ConclusionsThese 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.
- Published
- 2020