(A–C) LC electrical-stimulation-induced LTD of CeA IPSCs was significantly diminished by the α1AR antagonist HEAT (2 μM, A), but not by the combination of mGluR1 and mGluR5 antagonists MPEP (10 μM) and CPCCOEt (25 μM) (MP+CP, B). Summary in (C).
(D) Scatterplot of EPSC and PIC amplitudes of LC synapses on PBN (n = 30 cells from 22 animals). Highlights are PBN neurons that received high glutamate but low NA release or receptor activation.
(E) Two example PBN neurons with strong EPSCs but weak PICs. MP+CP blocked LTD, but HEAT did not.
(F–H) In a subset of PBN neurons with weak PICS (<20 pA), MP+CP blocked LTD (F). In a subset of PBN neurons with strong EPSCs (>80 pA), HEAT failed to block LTD (G). Summary in (H).
(I) Example images showing the variability of TH and eYFP (TH+vGlut2) expression in TH-flp;vGlut2-cre animals injected with AAV-hSyn-Con/Fon-ChR2-eYFP into the LC.
(J–M) Activation of mGluR-I with DHPG (100 μM, J) or α1ARs with Phe (10 μM, K) induced labile eCB-LTD, whereas activation of both receptors with DHPG+Phe (L) induced static eCB-LTD of CeA IPSCs. Summary in (M).
(N) Cartoon showing LC activates both α1ARs and mGluR-I in PBN neurons, which synergize to induce eCB-LTD at the CeA synapses on PBN.
Scale bars: 40 ms, 100 pA in (A), (B), (F), (G), and (J)–(L); 10 μm in (I). Statistics: *p ≤ 0.05, **p ≤ 0.005, ***p ≤ 0.001, ****p ≤ 0.0001, Kruskal Wallis with Dunn’s correction. Also see Figure S7 and Table S1.