The endogenous opioid peptides, met- or leu-enkephalin, and corticotropin-releasing factor (CRF) regulate noradrenergic neurons in the locus coeruleus (LC) in a convergent manner via projections from distinct brain areas. In contrast, the opioid peptide dynorphin (DYN) has been shown to serve as a co-transmitter with CRF in afferents to the LC. To further define anatomical substrates targeting noradrenergic neurons by DYN afferents originating from limbic sources, anterograde tract-tracing of biotinylated dextran amine (BDA) from the central amygdaloid complex was combined with immunocytochemical detection of DYN and tyrosine hydroxylase (TH) in the same section of tissue. Triple labeling immunocytochemistry was combined with electron microscopy in the LC where BDA was identified using an immunoperoxidase marker, and DYN and TH were distinguished by the use of sequential immunogold labeling and silver enhancement to produce different sized gold particles. Results show direct evidence of a monosynaptic pathway linking amygdalar DYN afferents with LC neurons. To determine whether DYN-containing amygdalar LC-projecting neurons colocalize CRF, retrograde tract-tracing using fluorescent latex microspheres injected into the LC was combined with immunocytochemical detection of DYN and CRF in single sections in the central amygdala. Retrogradely labeled neurons from the LC were distributed throughout the rostro-caudal extent of the central nucleus of the amygdala (CeA) as previously described. Cell counts showed that approximately 42% of LC-projecting neurons in the CeA contained both DYN and CRF. Taken with our previous studies showing monosynaptic projections from amygdalar CRF neurons to noradrenergic LC cells, the present study extends this by showing that DYN and CRF are co-transmitters in monosynaptic projections to the LC and are poised to coordinately impact LC neuronal activity. (C) 2011 Elsevier Inc. All rights reserved.
Amygdalar peptidergic circuits regulating noradrenergic locus coeruleus neurons: Linking limbic and arousal centers
Creators
B. A. S. Reyes - Jefferson Hospital for Neuroscience
A. F. Carvalho - Thomas Jefferson University
K. Vakharia - Thomas Jefferson University
E. J. Van Bockstaele - Thomas Jefferson University
Publication Details
Experimental neurology, v 230(1), pp 96-105
Publisher
Elsevier
Number of pages
10
Grant note
R29DA009082 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
DA 09082 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
Resource Type
Journal article
Language
English
Academic Unit
Pharmacology and Physiology
Web of Science ID
WOS:000291906300012
Scopus ID
2-s2.0-79958027311
Other Identifier
991021903289804721
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