FP medial dopamine neurons also commonly T0901317 web exhibited a tiny or undetectable
FP medial dopamine neurons also generally exhibited a compact or undetectable Ih, with cumulative probability profiles incredibly similar to their glutamatergic nondopamine neighbors (Fig. 2B). As a result, the expression of a smaller Ih ( 25 pA) cannot be utilized to distinguish medial dopamine from PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/18686015 glutamate only neurons, plus the absence of Ih can not be applied to exclude a dopaminergic phenotype, at the very least inside the medial VTA in the mouse (Lammel et al 2008; Zhang et al 200). In contrast, RFP dopamine neurons within the lateral VTA ordinarily displayed a considerably bigger Ih (Fig. 2A ). To assess simple membrane properties, we measured initial membrane prospective, Vm, initial firing rate, and action prospective (AP) waveforms in wholecell existing clamp. Relative to neighboring dopamine neurons, medial VTA glutamate neurons have been only slightly more hyperpolarized at rest and exhibited only a slightly shorter AP duration (Table ). However, medial dopamine neurons showed a substantially smaller sized afterhyperpolarization (AHP) following the AP than lateral dopamine neurons. Certainly, lateral VTA neurons normally exhibited each a larger and much more prolonged AHP than medial dopamine or glutamate only neurons (Table ). D2 dopamine receptors inside the VTA are generally thought to function as autoreceptors, responding to somatodendritically released dopamine and thereby inhibiting the activity of dopamine neurons (Johnson and North, 992b). Nonetheless, D2 receptor activation has 
also been reported to inhibit a lot of nondopamine VTA neurons (Cameron et al 997; Margolis et al 2006; Luo et al 200). We thus tested the sensitivity of VTA glutamateonly neurons to D2 receptor stimulation, working with bath application from the D2 agonist quinpirole ( M). Each medial glutamate only (Fig. 3A) and medial dopamine neurons (Fig. 3B) exhibited heterogeneous responses to quinpirole, with 42 (52 medial dopamine and 52 glutamate neurons) displaying inhibition by withincell paired t test, but other people showed either no impact or perhaps depolarization (medial dopamine neurons showed a mean change in Vm of 0. .2 mV; medial glutamate neurons, 0.3 2.4 mV). In contrast, quinpirole inhibited 70 of lateral dopamine neurons (p 0.05 by twotailed withincell paired t test); using a imply reduction in Vm of four.0 .eight mV (F(,9) four.86, p 0.055 by repeatedmeasures ANOVA) (Fig. 3C). As a result, both medial VTA glutamate only and dopamine neurons are less reliably inhibited by D2 receptor stimulation than much more lateral dopamine neurons. VTA glutamate neurons project to ventral striatum, PFC, amygdala, ventral pallidum, and lateral habenula To identify the projection targets of VTA glutamate neurons, we took benefit of a conditional adenoassociated virus (AAV) expressing ChR2mCherry (Fig. B). Just after activation by Cre recombinase, the ChR2mCherry labels axons and terminals, as well as cell bodies (Tsai et al 2009), to ensure that the injection of5080 J. Neurosci October 24, 202 32(43):5076 Hnasko et al. Properties and Projections of VTA Glutamate Neuronsboth TH (73 , n 45) and TH mCherry glutamatergic fibers in the PFC (Fig. 4 A, B), though both the dopaminergic and glutamatergic projection from midbrain appear significantly weaker in mice than in rat. Furthermore, mCherry fibers have been observed in the amygdala (Fig. 5C). Thus, VTA glutamatergic neurons project to quite a few from the very same regions exactly where dopamine is also released. We also observed dense mCherry fibers in two structures not identified to receive sturdy dopaminergic input. Initially, several mCherry fibers were observed inne.