(A) A virus promoting the expression of ChR2 was injected into the MDT of young mice. Acute brain slices containing the PFC were prepared 3-5 weeks later and op-EPSCs were elicited on isolated layer 5 PFC pyramidal cells. (B) Representative experiment illustrating LTD at thalamocortical synapses following bath application of LY379268 (LY268; 200 nM), an mGlu2/3 orthosteric agonist. (C) Averaged time courses showing robust LTD at MDT-PFC synapses (24 ± 3% baseline, n/N = 7/6 cells/mice per group). (D) VU6001966 (VU966; 3 μM), an mGlu2 NAM, partially inhibited LTD (64 ± 15% baseline, n/N = 7/3). Black lines display control data from panel C. (E) The mGlu3 NAM VU0650786 (VU786; 10 μM) partially inhibited LTD induction (64 ± 8% baseline, n/N = 6/4). (F) Bath application of LY341495, an mGlu2/3 orthosteric antagonist, completely blocked LTD expression (100 ± 6% baseline, n/N = 5/2). (G) Summary of last 10 minutes of each recording (ANOVA main effect of drug: F3,21 = 9.3, p<0.004; *: p<0.05, ***: p<0.001, Bonferonni post-test vs. control).