FP medial dopamine neurons also typically exhibited a little or undetectable
FP medial dopamine neurons also generally exhibited a little or undetectable Ih, with cumulative probability profiles really similar to their glutamatergic nondopamine neighbors (Fig. 2B). Thus, the expression of a compact Ih ( 25 pA) can not be employed to distinguish medial dopamine from PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/18686015 glutamate only neurons, as well as the absence of Ih can not 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 in the lateral VTA normally displayed a much larger Ih (Fig. 2A ). To assess standard membrane properties, we measured initial membrane possible, Vm, initial firing rate, and action prospective (AP) waveforms in wholecell present clamp. Relative to neighboring dopamine neurons, medial VTA glutamate neurons had been only slightly additional hyperpolarized at rest and exhibited only a slightly shorter AP duration (Table ). Even so, medial dopamine neurons showed a substantially smaller sized afterhyperpolarization (AHP) following the AP than lateral dopamine neurons. Indeed, lateral VTA neurons usually exhibited each a bigger and much more prolonged AHP than medial dopamine or glutamate only neurons (Table ). D2 dopamine receptors in the VTA are frequently believed to function as autoreceptors, responding to somatodendritically released dopamine and thereby inhibiting the activity of dopamine neurons (Johnson and North, 992b). On the other hand, 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, applying bath application of 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) showing inhibition by withincell paired t test, but other people showed either no effect or perhaps depolarization (medial dopamine neurons showed a mean change in Vm of 0. .2 mV; medial glutamate neurons, 0.3 two.4 mV). In contrast, quinpirole inhibited 70 of lateral dopamine neurons (p 0.05 by twotailed withincell paired t test); with a 
mean reduction in Vm of 4.0 .8 mV (F(,9) 4.86, p 0.055 by repeatedmeasures ANOVA) (Fig. 3C). As a result, both 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). Immediately after activation by Cre recombinase, the ChR2mCherry labels axons and terminals, along with cell bodies (Tsai et al 2009), so 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 within the PFC (Fig. four A, B), though both the dopaminergic and glutamatergic projection from midbrain appear a great deal weaker in mice than in rat. Furthermore, mCherry fibers have been observed in the amygdala (Fig. 5C). Therefore, VTA glutamatergic neurons project to many in the same order BMS-687453 regions where dopamine can also be released. We also observed dense mCherry fibers in two structures not recognized to obtain powerful dopaminergic input. 1st, a lot of mCherry fibers were observed inne.
