Neuronal projections from ventral tegmental area to forebrain structures in rat studied by manganese-enhanced magnetic resonance imaging

Abstract

Manganese-enhanced magnetic resonance imaging (MEMRI) has been widely applied to trace neuronal tracts and to monitor morphological and functional responses of specific brain circuits to changes in physiological and/or environmental conditions. In this study, we traced the efferent axonal projections from ventral tegmental area (VTA) to forebrain structures, an integrating part of the reward circuit implicated in drug addiction, in rats using MEMRI. Urethane- and chloral hydrate-anesthetized rats received injection of 100 nl of 200 mM MnCl(2) solution into the right VTA. Mn(2+)-induced signal enhancements were monitored 24 h after injection. The dose of MnCl(2) injection was shown, by histological evaluation, to have minor toxic effects to the neurons in/near the injection site. Dynamic Mn(2+)-induced signal intensity changes in urethane-anesthetized rats during a 24-h period were fit to a sigmoidal function to obtain parameters slope and t(50), which describe the dynamics of apparent Mn(2+)accumulation. The results showed that most of the forebrain structures known to receive neuronal projections from the VTA, including prefrontal cortex, nucleus accumbens, globus pallidus and caudate putaman, were enhanced at 24 h after injection of MnCl(2) into the ipsilateral VTA, and anesthesia seemed have little effects on the amount of Mn(2+)being transported from the VTA to these structures.