Afferents of the ventral tegmental area in the rat-anatomical substratum for integrative functions.

The ventral tegmental area (VTA) is critically important to an organism's capacity to detect rewards and novelty and to enlist appropriate behavioral responses. Although there has been substantial progress concerning information processing at the single cell and molecular levels in the VTA, our knowledge of its overall afferent connections is based principally on the benchmark description by Phillipson ([1979] J. Comp. Neurol. 187:117-144). Given that, since then, the sensitivity of tracing methods and knowledge about the organization of brain structures have increased considerably, we undertook to reevaluate the VTA afferents of the rat. The retrograde tracer Fluoro-Gold was injected into different parts of the VTA, and labeled neurons were visualized by immunocytochemistry. Retrogradely labeled neurons were not confined to nuclei but rather constituted an elongated formation stretching from the prefrontal cortex rostrally to the medulla oblongata caudally. In the case of descending afferents, this formation was centered on the medial forebrain bundle and the fasciculus retroflexus. The input to the VTA in general was bilateral, with a smaller descending and comparable ascending projection from the contralateral side. Injections of the anterograde tracers Phaseolus vulgaris-leucoagglutinin or biotinylated dextran amine into selected forebrain structures revealed a surprisingly sparse terminal arborization in the VTA. Furthermore, structures projecting to the VTA innervate other brain areas with similar or greater robustness, which in turn also provide a strong input to the VTA, indicating an anatomical network. Given the importance of the VTA in basic behaviors, this organization might provide a basis for an extraordinary level of afferent integration. (c) 2005 Wiley-Liss, Inc.