, 2010 and Bromberg-Martin et al., 2010). In rodents, for example, some VTA DA neurons are phasically excited by aversive stimuli (Mantz et al., 1989 and Brischoux et al., 2009). In nonhuman primates, DA neurons in the VTA and dorsolateral substantia nigra pars compacta (SNc)

also can encode aversive events and cues predicting such events as well as other features of stimuli including their motivational salience (Matsumoto and Hikosaka, 2009 and Bromberg-Martin et al., 2010). ATM Kinase Inhibitor manufacturer These findings have led to the proposal that DA neurons play a variety of critical roles in motivational control in addition to their importance for encoding reward prediction errors (Berridge et al., 2009: Bromberg-Martin et al., 2010 and Ungless et al., 2010). Consistent with the view that midbrain DA cells are not homogeneous are recent findings that the specific molecular and physiological properties of midbrain DA cells are associated with the target structures Tofacitinib order to which they project (Lammel et al., 2008 and Margolis

et al., 2008). A subgroup of “unconventional” DA neurons with high-frequency firing (>10 Hz) and low DA reuptake capacity (i.e., low dopamine transporter [DAT]/tyrosine hydroxylase [TH] expression ratio) is located in the medial posterior VTA and projects to the medial prefrontal cortex (mPFC), NAc core or NAc medial shell (Lammel et al., 2008). In contrast, “conventional” DA neurons with low-frequency firing (<10 Hz) are located in the lateral VTA and SNc and project to NAc lateral shell and dorsal striatum, respectively (Lammel et al., 2008). These findings raise the important question of whether the in vivo synaptic modulation and functional responses

of DA cells to different stimuli may be associated with the distinct anatomical target sites see more to which they project. Addressing this question is challenging because it requires unequivocal identification of the specific target area to which an identified DA cell projects. To begin to address this issue, we took advantage of the increase in excitatory synaptic strength on VTA DA neurons caused by passive administration or self-administration of drugs of abuse (Ungless et al., 2001, Saal et al., 2003, Borgland et al., 2004, Dong et al., 2004, Faleiro et al., 2004, Liu et al., 2005, Bellone and Lüscher, 2006, Argilli et al., 2008, Engblom et al., 2008, Stuber et al., 2008, Chen et al., 2008 and Heikkinen et al., 2009). Specifically, we visually identified and recorded from subpopulations of VTA and SNc DA neurons projecting to different target structures in acute midbrain slices by injecting fluorescent Retrobeads into the mPFC, the NAc medial shell, the NAc lateral shell, or the dorsolateral striatum of 3-month-old adult C57BL/6 mice (Lammel et al., 2008).