Functional implications of glutamatergic projections to the ventral tegmental area

Glutamatergic afferents of the ventral tegmental area (VTA) play an important role in the functioning of the VTA and are involved in the pathophysiology of drug addiction. It has recently been demonstrated that the VTA is densely innervated by glutamatergic axons and that glutamatergic neurons projecting to the VTA are situated in almost all structures that project there. While the projection from the prefrontal cortex is essentially entirely glutamatergic, subcortical glutamatergic neurons innervating the VTA intermingle with non-glutamatergic, most likely GABAergic and/or peptidergic VTA-projecting neurons. The first part of this review focuses on the origins and putative functional implications of various glutamatergic projections to the VTA. In the second part we consider how different neuropeptides via different mechanisms modulate glutamatergic actions in the VTA. We conclude by developing a model of how the glutamatergic afferents might together contribute to the functions of the VTA.