Rothem Kovner1, Tade Souaiaia2, Andrew S Fox3, Delores A French4, Cooper E Goss5, Patrick H Roseboom6, Jonathan A Oler4, Marissa K Riedel4, Eva M Fekete4, Julie L Fudge7, James A Knowles2, Ned H Kalin8. 1. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin-Madison, Madison, Wisconsin. Electronic address: kovnerrothem@gmail.com. 2. Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York. 3. Department of Psychology, University of California, Davis, Davis, California; California National Primate Research Center, University of California, Davis, Davis, California. 4. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin-Madison, Madison, Wisconsin. 5. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin. 6. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin-Madison, Madison, Wisconsin. 7. Department of Psychiatry, University of Rochester Medical Center, Rochester, New York; Department of Neuroscience/Del Monte Institute for Brain Research, University of Rochester Medical Center, Rochester, New York. 8. Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin; Neuroscience Training Program, University of Wisconsin-Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin-Madison, Madison, Wisconsin. Electronic address: nkalin@wisc.edu.
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.
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 humananxiety, and points to specific molecules within this circuit that could serve as potential treatment targets for anxiety disorders.
Keywords:
Anxiety; Bed nucleus of the stria terminalis; Central nucleus of the amygdala; Fear; Microcircuitry; Protein kinase C delta (PKCδ); Retrograde tracing; Somatostatin; Stress
Authors: Nathan A Fox; Heather A Henderson; Peter J Marshall; Kate E Nichols; Melissa M Ghera Journal: Annu Rev Psychol Date: 2005 Impact factor: 24.137
Authors: Andrew S Fox; Jonathan A Oler; Steven E Shelton; Steven A Nanda; Richard J Davidson; Patrick H Roseboom; Ned H Kalin Journal: Proc Natl Acad Sci U S A Date: 2012-10-15 Impact factor: 11.205