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The Journal of Neuroscience, May 23, 2007, 27(21):5730-5743; doi:10.1523/JNEUROSCI.0012-07.2007

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Behavioral/Systems/Cognitive
Glutamatergic Afferents of the Ventral Tegmental Area in the Rat

Stefanie Geisler,¹ Christian Derst,² Rüdiger W. Veh,² and Daniel S. Zahm¹

¹Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104, and ²Institute for Integrative Neuroanatomy, Charité Universtiätsmedizin Berlin, 10098 Berlin, Germany

Correspondence should be addressed to either of the following: Dr. Stefanie Geisler, National Institute on Drug Abuse, Intramural Research Program, Behavioral Neuroscience Branch, Building C, 5500 Nathan Shock Drive, Baltimore, MD 21224, Email: GeislerS{at}mail.nih.gov; or Dr. Daniel S. Zahm, Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1411 South Grand Boulevard, St. Louis, MO 63104, Email: zahmds{at}slu.edu

Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial to the capacity of the VTA to detect and signal stimulus salience, have been reported to arise in but a few structures. However, the afferent system of the VTA comprises very abundant neurons within a large formation extending from the prefrontal cortex to the caudal brainstem. Neurons in nearly all parts of this continuum may be glutamatergic and equivalently important to VTA function. Thus, we sought to identify the full range of glutamatergic inputs to the VTA by combining retrograde transport of wheat germ agglutinin-bound gold after injections into the VTA with nonisotopic in situ hybridization of the vesicular glutamate transporters (VGLUTs) 1, 2, and 3. We found glutamatergic neurons innervating the VTA in almost all structures projecting there and that a majority of these are subcortical and VGLUT2 mRNA positive. The tremendous convergence of glutamatergic afferents from many brain areas in the VTA suggests that (1) the function of the VTA requires integration of manifold and diverse bits of information and (2) the activity of the VTA reflects the ongoing activities of various combinations of its afferents.

Key words: VTA; excitatory; VGLUT; connections; hypothalamus; reward

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Received Jan. 3, 2007; revised April 23, 2007; accepted April 23, 2007.

Correspondence should be addressed to either of the following: Dr. Stefanie Geisler, National Institute on Drug Abuse, Intramural Research Program, Behavioral Neuroscience Branch, Building C, 5500 Nathan Shock Drive, Baltimore, MD 21224, Email: GeislerS{at}mail.nih.gov; or Dr. Daniel S. Zahm, Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1411 South Grand Boulevard, St. Louis, MO 63104, Email: zahmds{at}slu.edu

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