Rvating the rostrocaudal extent with the ventral pallidum, VP (Fig. 5 ARvating the rostrocaudal extent

Rvating the rostrocaudal extent with the ventral pallidum, VP (Fig. 5 A
Rvating the rostrocaudal extent from the ventral pallidum, VP (Fig. 5 A, B). In rostral (+)-Bicuculline coronal sections, these fibers innervate the “fingerlike” extensions from the VP discovered ventral to the NAc and dorsal for the olfactory tubercle (Fig. 4 A, C,E). Second, we observed dense innervation with the lateral habenula (LHb) (Fig. 5D). Greater than 98 of mCherry fibers in these regions lacked TH staining; PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/11836068 as a result, VTA projections to the VP and LHb appear to release only glutamate. Even though it remains feasible that glutamate only neurons do the truth is store and release dopamine but fail to express detectable levels of TH, the outcomes recommend that they nonetheless represent a novel population that has previously escaped observation. VTA glutamate neurons form excitatory synapses within the nucleus accumbens and ventral pallidum To decide whether or not VGLUT2 projections from the VTA kind functional excitatory synapses, we employed light to stimulate terminals expressing ChR2mCherry right after stereotactic injection of the conditional AAV in to the midbrain of VGLUT2Cre mice. Given that stereotactic injection with the same virus into DATCre mice confers VGLUT2dependent, lightevoked excitatory responses in the NAc (Stuber et al 200; Tecuapetla et al 200), we have been not surprised to see lightevoked currents in the very same region of VGLUT2Cre mice (Fig. 6 A). Indeed, optically evoked excitatory connections had been observed in all cells surrounded by fibers robustly expressing mCherry and had been not present in regions devoid of mCherry fibers. The peak amplitude of lightevoked currents when held at 70 mV averaged 39 five pA (n 2) and showed sensitivity to DNQX, indicating AMPARmediated currents (Fig. six B, C). Also, when held at 40 mV, light evoked NmethylDaspartate receptor (NMDAR)mediated currents in medium spiny neurons of your medial shell of the NAc (Fig. 6 A). Further, some neurons showed outward IPSCs in response to light stimulation when the neuron was held at 0 mV. These IPSCs have been blocked by either the Cl channel blocker picrotoxin or the GABAA receptor antagonist gabazine (information not shown) and had delayed onsets, consistent using the activation of polysynaptic circuits (Fig. 6 A). To characterize the novel projection from VTA to VP, we recorded the response of VP neurons to optical stimulation with the ChR2mCherry terminals derived from VGLUT2 VTA neurons. Again, we discovered each AMPAR and NMDARmediated currents (Fig. 6 D), with peak AMPAR currents averaging 4 0 pA (n 22) and sensitive to DNQX (Fig. six E, F ). VGLUT2expressing nondopamine neurons within the VTA hence type functional excitatory synapses within the VP. We also observed IPSCs in some VP neurons when holding the cell at 0 mV. As inside the NAc, these currents had been sensitive to picrotoxin and gabazine, even though the synaptic delay was significantly shorter than that observed inside the NAc, raising the possibility of GABA release by VGLUT2 neurons.Figure 3. Response to D2 dopamine receptor (D2R) activation differs among medial glutamate, medial dopamine, and lateral dopamine VTA neurons. A, A2, A VTA glutamate neuron hyperpolarizes in response to quinpirole (A), but a scatter plot distribution of responses shows that VTA glutamate neurons respond heterogeneously to D2R agonist application (A2). B, B2, A medial VTA dopamine neuron doesn’t respond to quinpirole (B), however the distribution shows similarly heterogeneous responsiveness to D2 stimulation by medial VTA dopamine neurons (B2). C, C2, Lateral VTA dopamine neurons hyperpolarize in response to quinpiro.