Figure 2.

mGluR5 and CB1R in D1 Neurons Mediate eCB-LTD

(A) Genetic downregulation of mGluR5 selectively in D1-MSNs abolishes eCB-mediated long-term depression in the NAc. Average time courses of mean EPSC (represented as percentage of the basal value) showing that in NAc slices prepared from wild-type (WT) and D1^miRmGluR5 mice, low-frequency stimulation (10 min 10 Hz, indicated by arrow) induced LTD in WT (n = 6, blue circles) but not in D1^miRmGluR5 mice (n = 16, red circles). Error bars indicate SEM, n = individual mouse. Adjacent to the timecourse, individual experiments (blue and red symbols) and group average (black symbols) before (baseline) and after LTD induction are shown. LTD was present in slices from WT mice (on the left) but in contrast, LTD was absent in D1^miRmGluR5 mice (on the right). Error bars indicate SEM, n = individual mouse, ∗p < 0.05, Mann-Whitney U-test.

(B) eCB-LTD is induced in MSNs from both the direct (D1 red) and indirect (D2 orange) pathways in wild-type mice. Retrogradely labeled direct and indirect pathway MSNs (see methods) were visualized by IR-DIC/epifluorescence microscopy and patch clamped.

(C) In D1^miRmGluR5 mice, eCB-LTD is selectively abolished in D1+ neurons, as 10-min Hz stimulation (arrow) induces LTD only in D1− (presumably D2+) NAc MSNs (empty red symbols) but is absent in D1+ neurons (filled red circles).

(D) In contrast, bath application of the specific mGluR2/3 agonist, LY379268 (100nM), induces a profound LTD of fEPSP of similar amplitude in NAc of wild-type or D1^miRmGluR5 mice. Average time courses of mean EPSC/fEPSP are represented as percentage of basal value.