We also examined whether an aversive stimulus affected these same sets of synapses in a similar manner. Our results suggest that the long-lasting modulation of synapses on DA cells caused in vivo by rewarding and aversive stimuli is not uniform but rather differs dramatically depending on Dasatinib chemical structure the respective target structures to which DA neurons project. Most previous in vitro electrophysiological studies of

midbrain DA neurons appear to have targeted DA neurons in the anterior lateral VTA, predominantly the parabrachial pigmented nucleus (PBP) (Brischoux et al., 2009 and Ungless et al., 2010). In addition, putative DA cells were commonly identified by the presence of a large hyperpolarization-activated current (Ih) while cells that lacked this current were considered nondopaminergic (Ungless et al., 2001, Gutlerner et al., 2002, Saal et al., 2003, Borgland et al., 2004, Faleiro et al., 2004, Bellone and Lüscher, 2006, Margolis et al., 2006, Hommel et al., 2006, Argilli et al., 2008, Stuber et al., 2008 and Zweifel et al., 2008) even though Volasertib purchase this criterion does not unequivocally identify DA neurons

(Johnson and North, 1992, Ford et al., 2006, Margolis et al., 2006, Margolis et al., 2008 and Zhang et al., 2010a). Therefore, one major goal of this study was to identify and record from DA cell subpopulations that have largely been neglected. By using in vivo Retrobead injections to identify the projection target of individual DA neurons, we first determined the percentage of retrogradely labeled neurons in the posterior VTA that are dopaminergic as defined by immunoreactivity for TH. Injections were made in the mPFC, NAc medial shell, and NAc lateral shell to label VTA DA neurons as well as the dorsolateral striatum for labeling of nigrostriatal aminophylline DA cells (Figure 1A).

In agreement with previous results (Lammel et al., 2008) we found that retrogradely labeled neurons that project to the mPFC and medial shell of the NAc are mainly located in the medial posterior VTA, medial paranigral nucleus and adjacent medial aspects of the PBP nucleus (Figure 1B). In contrast, neurons that project to the lateral shell of the NAc were located in the lateral VTA, mainly in the lateral PBP nucleus. Nigrostriatal neurons were almost exclusively found in the SNc. Approximately 80%–95% of the retrogradely labeled cells in the posterior VTA and SN also were immunopositive for TH indicating that they were dopaminergic (Figure 1C, n = 49–140 cells for each group). Recordings from retrogradely labeled neurons revealed significant differences in the magnitude of Ih depending on the neurons’ projection targets. Cells projecting to the mPFC or NAc medial shell exhibited an Ih that was dramatically smaller than those recorded from neurons projecting to the NAc lateral shell or dorsal striatum (Figures 1D and 1E, mesocortical neurons: 24.2 ± 9.4 pA, n = 8; mesolimbic medial shell neurons: 10.7 ± 0.