FP medial dopamine neurons also frequently exhibited a modest or undetectable
FP medial dopamine neurons also commonly exhibited a compact or undetectable Ih, with cumulative probability profiles really related to their glutamatergic nondopamine neighbors (Fig. 2B). Therefore, the Astringenin expression of a compact Ih ( 25 pA) cannot be applied to distinguish medial dopamine from PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/18686015 glutamate only neurons, and also the absence of Ih can’t be employed to exclude a dopaminergic phenotype, 
at the least within the medial VTA with the mouse (Lammel et al 2008; Zhang et al 200). In contrast, RFP dopamine neurons within the lateral VTA commonly displayed a substantially bigger Ih (Fig. 2A ). To assess standard membrane properties, we measured initial membrane potential, Vm, initial firing price, and action prospective (AP) waveforms in wholecell existing clamp. Relative to neighboring dopamine neurons, medial VTA glutamate neurons have been only slightly a lot more hyperpolarized at rest and exhibited only a slightly shorter AP duration (Table ). Nevertheless, medial dopamine neurons showed a substantially smaller sized afterhyperpolarization (AHP) following the AP than lateral dopamine neurons. Certainly, lateral VTA neurons generally exhibited each a larger and more prolonged AHP than medial dopamine or glutamate only neurons (Table ). D2 dopamine receptors inside the VTA are normally 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 several nondopamine VTA neurons (Cameron et al 997; Margolis et al 2006; Luo et al 200). We for that reason tested the sensitivity of VTA glutamateonly neurons to D2 receptor stimulation, utilizing bath application in 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 effect or perhaps depolarization (medial dopamine neurons showed a mean modify in Vm of 0. .2 mV; medial glutamate neurons, 0.three 2.four 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 4.0 .eight mV (F(,9) four.86, p 0.055 by repeatedmeasures ANOVA) (Fig. 3C). Therefore, each medial VTA glutamate only and dopamine neurons are significantly less reliably inhibited by D2 receptor stimulation than far more lateral dopamine neurons. VTA glutamate neurons project to ventral striatum, PFC, amygdala, ventral pallidum, and lateral habenula To determine the projection targets of VTA glutamate neurons, we took advantage of a conditional adenoassociated virus (AAV) expressing ChR2mCherry (Fig. B). Following activation by Cre recombinase, the ChR2mCherry labels axons and terminals, as well as cell bodies (Tsai et al 2009), in order 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. four A, B), although each the dopaminergic and glutamatergic projection from midbrain appear considerably weaker in mice than in rat. Moreover, mCherry fibers had been observed within the amygdala (Fig. 5C). Therefore, VTA glutamatergic neurons project to quite a few with the same regions exactly where dopamine is also released. We also observed dense mCherry fibers in two structures not known to receive powerful dopaminergic input. 1st, a lot of mCherry fibers were observed inne.