caa a22 4500 606201092 CHVBK 20210128100946.0 cr unu---uuuuu 210128e20150101xx s 000 0 eng 10.1007/s00429-013-0674-8 doi (NATIONALLICENCE)springer-10.1007/s00429-013-0674-8 Direct targeting of peptidergic amygdalar neurons by noradrenergic afferents: linking stress-integrative circuitry [Elektronische Daten] [J. Kravets, B. Reyes, E. Unterwald, E. Van Bockstaele] Amygdalar norepinephrine (NE) plays a key role in regulating neural responses to emotionally arousing stimuli and is involved in memory consolidation of emotionally charged events. Corticotropin-releasing factor (CRF) and dynorphin (DYN), two neuropeptides that mediate the physiological and behavioral responses to stress, are abundant in the central nucleus of the amygdala (CeA), and directly innervate brainstem noradrenergic locus coeruleus (LC) neurons. Whether the CRF- and DYN-containing amygdalar neurons receive direct noradrenergic innervation has not yet been elucidated. The present study sought to define cellular substrates underlying noradrenergic modulation of CRF- and DYN-containing neurons in the CeA using immunohistochemistry and electron microscopy. Ultrastructural analysis revealed that NE-labeled axon terminals form synapses with CRF- and DYN-containing neurons in the CeA. Semi-quantitative analysis showed that approximately 31% of NET-labeled axon terminals targeted CeA neurons that co-expressed DYN and CRF. As a major source of CRF innervation to the LC, it is also not known whether CRF-containing CeA neurons are directly targeted by noradrenergic afferents. To test this, retrograde tract tracing using FluoroGold from the LC was combined with immunocytochemical detection of CRF and NET in the CeA. Our results revealed a population of LC-projecting CRF-containing CeA neurons that are directly innervated by NE afferents. Analysis showed that approximately 34% of NET-labeled axon terminals targeted LC-projecting CeA neurons that contain CRF. Taken together, these results indicate significant interactions between NE, CRF and DYN in this critical limbic region and reveal direct synaptic interactions of NE with amygdalar CRF that influence the LC-NE arousal system. Springer-Verlag Berlin Heidelberg, 2013 Amygdala nationallicence Norepinephrine nationallicence Corticotropin-releasing factor nationallicence Dynorphin nationallicence Locus coeruleus nationallicence Kravets J. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut Reyes B. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut Unterwald E. Department of Pharmacology, Center for Substance Abuse Research, Temple University School of Medicine, 19140, Philadelphia, PA, USA aut Van Bockstaele E. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 541-558 1863-2653 220:1<541 2015 220 429 https://doi.org/10.1007/s00429-013-0674-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-013-0674-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kravets J. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Reyes B. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Unterwald E. Department of Pharmacology, Center for Substance Abuse Research, Temple University School of Medicine, 19140, Philadelphia, PA, USA aut NATIONALLICENCE 700 1- Van Bockstaele E. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 S. 15th Street, 19102, Philadelphia, PA, USA aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/1(2015-01-01), 541-558 1863-2653 220:1<541 2015 220 429