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The Journal of Neuroscience, March 18, 2009, 29(11):3613-3626; doi:10.1523/JNEUROSCI.4632-08.2009

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Behavioral/Systems/Cognitive
Adrenergic and Noradrenergic Innervation of the Midbrain Ventral Tegmental Area and Retrorubral Field: Prominent Inputs from Medullary Homeostatic Centers

Carlos A. Mejías-Aponte,¹ Candice Drouin,² and Gary Aston-Jones³

¹Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, ²Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, and ³Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425

Correspondence should be addressed to Dr. Gary Aston-Jones, Department of Neurosciences, Medical University of South Carolina, 403 BSB, 173 Ashley Avenue, Charleston, SC 29425. Email: astong{at}musc.edu

Adrenergic agents modulate the activity of midbrain ventral tegmental area (VTA) neurons. However, the sources of noradrenergic and adrenergic inputs are not well characterized. Immunostaining for dopamine β-hydroxylase revealed fibers within dopamine (DA) neuron areas, with the highest density in the retrorubral field (A8 cell group), followed by the VTA (A10 cell group), and very few fibers within substantia nigra compacta. A less dense, but a similar pattern of fibers was also found for the epinephrine marker, phenylethanolamine N-methyl transferase. Injection of the retrograde tracer wheat germ agglutinin-apo (inactivated) horseradish peroxidase conjugated to colloidal gold, or cholera toxin subunit b, revealed that the noradrenergic innervation of the A10 and A8 regions arise primarily from A1, A2, A5, and locus ceruleus neurons. Selective lesions of the ventral noradrenergic bundle confirmed a prominent innervation from A1 and A2 areas. Retrogradely labeled epinephrine neurons were found mainly in the C1 area. The identification of medullary noradrenergic and adrenergic afferents to DA neuron areas indicates new pathways for visceral-related inputs to reward-related areas in the midbrain.

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Received Sept. 26, 2008; revised Dec. 3, 2008; accepted Feb. 17, 2009.

Correspondence should be addressed to Dr. Gary Aston-Jones, Department of Neurosciences, Medical University of South Carolina, 403 BSB, 173 Ashley Avenue, Charleston, SC 29425. Email: astong{at}musc.edu

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