Figure 3.

OP-LTD requires M₁ and M₃ mAChR signaling, but does not require spontaneous neuronal activity or NMDAR currents. For all panels, statistical significances are determined between average fEPSP amplitudes during the final 5 min of baseline versus the final 5 min of treatment (indicated on plot) as well as between the final 5 min of treatment between vehicle and soman (bar graphs on right). (A) Non-specific mAChR antagonist atropine (ATR; 5 μM) blocks OP-LTD (n = 4 each; p = 0.36 versus baseline; p = 0.43 versus vehicle). (B) M₁ mAChR antagonist VU 0255035 (VU; 1 μM) blocks OP-LTD (n = 4 each; p = 0.52 versus baseline; p = 0.60 versus vehicle). (C) M2 mAChR antagonist AQ-RA (1 μM) does not prevent OP-LTD (n = 4 each; p = 0.003 versus baseline; p = 0.003 versus vehicle). (D) M3 mAChR antagonist 4-DAMP (100 nM) blocks OP-LTD (n = 4 each; p = 0.71 versus baseline; p = 0.62 versus vehicle). (E) M4 mAChR antagonist PD 102807 (PD; 500 nM) does not prevent OP-LTD (n = 3 each; p < 0.001 versus baseline; p < 0.001 versus vehicle). For A-E, perfusion with mAChR antagonists alone had no effect on fEPSP amplitudes (white circles, n ≥ 4 for each). Representative fEPSPs for baseline (black) and following treatment (blue) are shown as insets in each plot. Scale bars = 0.20 mV by 50 ms. (F) OP-LTD occurs despite incision of CA3 afferent fibers (n = 3 each; p = 0.011 versus baseline; p = 0.003 versus vehicle). (Inset) Coronal hippocampal slice with representative incision at the Schaffer collateral fibers. (G) APV does not prevent OP-LTD (n = 4 each; p = 0.007 versus baseline; p = 0.004 versus vehicle), even though (H) APV blocks high frequency-induced long-term potentiation (n = 3 each; p < 0.001 versus baseline; p = 0.003 versus vehicle).