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The Journal of Neuroscience, March 3, 2004, 24(9):2313-2321; doi:10.1523/JNEUROSCI.5339-03.2004

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Behavioral/Systems/Cognitive
Numerous GABAergic Afferents to Locus Ceruleus in the Pericerulear Dendritic Zone: Possible Interneuronal Pool

Gary Aston-Jones,¹ Yan Zhu,¹ and J. Patrick Card²

¹Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, and ²Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260

Most nuclei in the CNS are composed of principal neurons that project to other areas and interneurons that serve to integrate information among afferents. The noradrenergic brain nucleus locus ceruleus (LC) has appeared to be an exception to this general rule, because the LC is composed almost entirely of noradrenergic principal neurons. Here, we report that numerous small neurons in the peri-LC region become retrogradely labeled after focal injections of wheat germ agglutinin-apo (inactivated) horseradish peroxidase conjugated to colloidal gold, or pseudorabies virus (PRV), into the nuclear core of the rat LC. A substantial number of these neurons were routinely found within the dendritic field of the LC, in the area surrounding the compact cell-dense region classically defined as LC. Double labeling revealed that a large percentage of these cells stained for GABA. Ultrastructural analyses revealed axodendritic and axosomatic contacts between PRV-labeled afferents and LC neurons labeled with tyrosine hydroxylase immunohistochemistry. In addition, PRV-labeled neurons or axons were immunopositive for GABA in ultrastructural localizations. Analysis of the synaptology of immunopositive profiles demonstrated that these LC afferents in the peri-LC region receive several non-LC synaptic inputs. These results indicate that a population of small GABAergic neurons in the peri-LC dendritic zone may provide interneuronal integration for LC noradrenergic neurons.

Key words: norepinephrine; locus ceruleus; GABA; ultrastructure; interneurons; pseudorabies virus

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Received Dec 3, 2003; revised January 10, 2004; accepted January 14, 2004.

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