Figure 4.
Facilitation by 10-min 5-HT at nondepressed synapses involves presynaptic PKC, postsynaptic Ca2+ and CamKII, and type II or III metabotropic glutamate receptors. (A) Facilitation by 10 or 20 µM 5-HT (which have been pooled—black symbols) was significantly reduced by the PKC inhibitor Go6983 (n = 14) or the CamKII inhibitor KN93 (n = 10) but not by the PKA inhibitor KT5720 (n = 15), compared with DMSO control (n = 38). Test-alone depression (white symbols) is replotted from Figure 2A1. There was a significant overall drug × 5-HT interaction (F(6,103) = 4.41, P < 0.001). KT5720 had a greater effect on facilitation during 10 µM 5-HT (n = 6 and 18, insert). (B) Facilitation by 20 µM 5-HT was significantly reduced by presynaptic injection of a peptide inhibitor of PKC (n = 8) but not by peptide inhibitors of PKA (n = 5) or CamKII (n = 6), compared with vehicle control (n = 19). There was a significant overall group × vehicle/inhibitor interaction (F(2,32) = 2.85, P < 0.05 one-tail). The average pretest values for experiments with presynaptic injections in this figure and Figures 2A2 and 2B2 (in mV) were 6.8 ± 1.0 (vehicle), 10.7 ± 2.1 (PKA inhibitor), 7.4 ± 2.2 (PKC inhibitor), and 9.2 ± 3.2 (CamKII inhibitor), not significantly different. (C) The facilitation was significantly reduced by postsynaptic injection of BAPTA (n = 22) or a peptide inhibitor of CamKII (n = 5) but not by a peptide inhibitor of PKC (n = 7), compared with vehicle control (n = 34). There was a significant overall group × vehicle/inhibitor interaction (F(4,58) = 3.76, P < 0.01). The average pretest values for experiments with postsynaptic injections in this figure and Figure 2A2 and 2B3 (in mV) were 6.8 ± 0.7 (vehicle), 5.6 ± 0.9 (BAPTA), 6.5 ± 1.1 (PKC inhibitor), and 7.0 ± 3.0 (CamKII inhibitor), not significantly different. (D) The facilitation was significantly enhanced by the type II and III mGluR antagonist LY341495 (n = 7) compared with DMSO control (n = 6). There was a significant overall effect of group (F(1,11) = 3.97, P < 0.05 one tail). The average pretest values (in mV) were 12.9 ± 4.2 (control) and 9.9 ± 2.3 (LY341495), not significantly different.