Document Detail


Forebrain GABAergic projections to locus coeruleus in mouse.
MedLine Citation:
PMID:  23296594     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The noradrenergic locus coeruleus (LC) regulates arousal, memory, sympathetic nervous system activity, and pain. Forebrain projections to LC have been characterized in rat, cat, and primates, but not systematically in mouse. We surveyed mouse forebrain LC-projecting neurons by examining retrogradely labeled cells following LC iontophoresis of Fluoro-Gold and anterograde LC labeling after forebrain injection of biotinylated dextran amine or viral tracer. Similar to other species, the central amygdalar nucleus (CAmy), anterior hypothalamus, paraventricular nucleus, and posterior lateral hypothalamic area (PLH) provide major LC inputs. By using mice expressing green fluorescent protein in γ-aminobutyric acid (GABA)ergic neurons, we found that more than one-third of LC-projecting CAmy and PLH neurons are GABAergic. LC colocalization of biotinylated dextran amine, following CAmy or PLH injection, with either green fluorescent protein or glutamic acid decarboxylase (GAD)65/67 immunoreactivity confirmed these GABAergic projections. CAmy injection of adeno-associated virus encoding channelrhodopsin-2-Venus showed similar fiber labeling and association with GAD65/67-immunoreactive (ir) and tyrosine hydroxylase (TH)-ir neurons. CAmy and PLH projections were densest in a pericoerulear zone, but many fibers entered the LC proper. Close apposition between CAmy GABAergic projections and TH-ir processes suggests that CAmy GABAergic neurons may directly inhibit noradrenergic principal neurons. Direct LC neuron targeting was confirmed by anterograde transneuronal labeling of LC TH-ir neurons following CAmy or PLH injection of a herpes virus that expresses red fluorescent protein following activation by Cre recombinase in mice that express Cre recombinase in GABAergic neurons. This description of GABAergic projections from the CAmy and PLH to the LC clarifies important forebrain sources of inhibitory control of central nervous system noradrenergic activity.
Authors:
Eugene L Dimitrov; Yuchio Yanagawa; Ted B Usdin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  The Journal of comparative neurology     Volume:  521     ISSN:  1096-9861     ISO Abbreviation:  J. Comp. Neurol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-04-22     Completed Date:  2013-11-05     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0406041     Medline TA:  J Comp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2373-97     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Afferent Pathways / physiology*
Animals
Biotin / analogs & derivatives,  metabolism
Dextrans / metabolism
GABAergic Neurons / physiology*
Glutamate Decarboxylase / genetics,  metabolism
Green Fluorescent Proteins / genetics
Locus Coeruleus / physiology*
Mice
Mice, Inbred C57BL
Mice, Transgenic
Microscopy, Confocal
Nerve Tissue Proteins / metabolism
Prosencephalon / cytology*
Proteins / genetics,  metabolism
RNA, Untranslated
Stilbamidines / metabolism
Vesicular Inhibitory Amino Acid Transport Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
MH002685-16/MH/NIMH NIH HHS; ZIA MH002685-20/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; 0/Gt(ROSA)26Sor non-coding RNA, mouse; 0/Nerve Tissue Proteins; 0/Proteins; 0/RNA, Untranslated; 0/Stilbamidines; 0/Vesicular Inhibitory Amino Acid Transport Proteins; 0/Viaat protein, mouse; 0/biotinylated dextran amine; 147336-22-9/Green Fluorescent Proteins; 6SO6U10H04/Biotin; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 1; K3R6ZDH4DU/Dextrans
Comments/Corrections

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