Although the drug-evoked synaptic plasticity in VTA DA neurons is robust, recent studies have demonstrated that these cells are not homogeneous but instead exhibit different electrophysiological and molecular properties depending on the specific brain area to which they project (Lammel et al., 2008; Margolis et al., 2006). This distinction between different subtypes of VTA DA neurons may be important because the presence of a large Ih current has commonly been used as a feature to identify DA neurons yet, for example, VTA DA neurons projecting to the medial PFC and the amygdala lack Ih currents and also express low levels of DAT and D2 receptors. Indeed, recent work has found that these mesocortical DA neurons do not exhibit an increase in the AMPAR/NMDAR ratio following single or chronic administration of cocaine but do express an increase following a salient, but aversive stimulus (Lammel and Malenka, 2010). The exclusively DAergic nature of VTA projection neurons has also been questioned. Using optogenetic tools unambiguous functional evidence for co-release of DA and glutamate from VTA projection neurons has been provided (Tecuapetla et al.,
