Figure 4. mGlu₃-LTD is modulated by mGlu₅-Homer interactions and Glycogen synthase kinase 3.

(a) Inclusion of a peptide that blocks the interaction between metabotropic glutamate receptor subtype 5 (mGlu₅) and Homer proteins (mGlu₅-C-ter) in the patch pipette enhances mGlu₃-LTD (49.0 ± 7.5% baseline, n/N = 4/2 cells/mice) relative to a control peptide (mGlu₅-mut) that does not impair the mGlu₅-Homer interaction (73.2 ± 4.3% baseline, n/N = 5/4). (b) Whole-cell infusion of mGlu₅-C-ter generates LTD following threshold application of LY379268 (67.8 ± 5.6% baseline, n/N = 6/4), whereas inclusion of mGlu₅-mut in the pipette has no effect (93.6 ± 9.8% baseline, n/N = 6/4). (c) Summary of the last 10 minutes of the recordings from the timecourse experiments (*: p < 0.05, **: p < 0.01, t-tests). (d) The mechanistic target of rapamycin inhibitor KU-0063794 does not affect mGlu₃-LTD (69.2 ± 5.2% baseline, n/N = 7/5). Black lines in panels 4d-5f denote control experiments from figure 1b. (e) Blocking protein translation with anisomycin does not impair mGlu₃-LTD (62.7 ± 6.4% baseline, n/N = 6/6). (f) The glycogen synthase kinase 3 inhibitor CHIR 99203 blocks the induction of LTD (89.6 ± 11.0% baseline, n/N = 5/5). EPSC, excitatory postsynaptic current; LTD, long-term depression; mGlu₅, metabotropic glutamate receptor subtype 5.