Fig. 2: 5-HT-induced depression of the ACC-claustrum synapse: 5-HT1B dependence. | Nature Communications

Fig. 2: 5-HT-induced depression of the ACC-claustrum synapse: 5-HT1B dependence.

From: Serotonin and psilocybin activate 5-HT1B receptors to suppress cortical signaling through the claustrum

Fig. 2

A Diagram of whole-cell patch recordings with optogenetic stimulation of ACC terminals, corresponding to B–D. B CP-93129 (10 μM, 10 min), a specific 5-HT1B agonist, induced a depression of the ACC-claustrum synapse (two-tailed paired Student’s t-test, t10 = 4.81, p <.001, n = 11 neurons from 8 animals) that was blocked by SB-216641 (20 μM, 10 min), a specific 5-HT1B antagonist. C Top, comparison of the magnitude of oEPSC amplitude during the last five minutes of recording after 10 μM CP-39129 exposure (n = 11, from 8 animals) or 20 μM SB-216641 (n = 6, from 4 animals) (two-tailed Student’s t-test, t15 = 2.90, p = 0.01). Bottom, PPR significantly increased after exposure to 10 μM CP-93129 (two-tailed paired Student’s t-test, t7 = 2.43, p = 0.046, n = 8 neurons from 8 animals). D Representative oEPSC events during baseline and last five minutes of recording for both 10 μM CP-93129 exposed neurons (orange) and 10 μM CP-93129 in 20 μM SB-216641 exposed neurons (light brown). E Experimental diagram corresponding to F–H. F The 5-HT-induced depression of the ACC-claustrum synapse was blocked by 40 μM SB-216641. G Comparison of the magnitude of oEPSC amplitudes during the last five minutes of recording for 10 μM 5-HT exposed cells in normal aCSF (n = 7, from 7 animals) or 40 μM SB-216641 (n = 6, from 4 animals) (two-tailed Student’s t-test, t10 = 2.83, p = 0.01). H Representative oEPSC events during baseline and the last five minutes of recording for both 10 μM 5-HT (blue) and 10 μM 5-HT in 40 μM SB-216641 (light blue) conditions. I Top, experimental diagram corresponding to this panel. Middle, CP-93129 (10 μM, 10 min) did not induce a change in oEPSC amplitude while in the presence of GR-127935 (20 μM), a 5-HT1B/D antagonist (two-tailed paired Student’s t-test, t4 = 0.58, p = 0.59, n = 5 neurons from 3 animals). Bottom, representative oEPSC events during baseline and after exposure to CP-93129 (10 μM, 10 min) in GR-127935 (20 μM) aCSF. J Top, experimental diagram corresponding to this panel. Middle, CP-93129 (10 μM, 10 min) depressed the ACC-claustrum synapse in the presence of LY-310762 (10 μM), a selective 5-HT1D antagonist (two-tailed paired Student’s t-test, t4 = 5.89, p = 0.004, n = 5 neurons from 4 animals). Bottom, representative oEPSC events during baseline and after exposure to CP-93129 (10 μM, 10 min) in LY-310762 (10 μM). K Top, experimental diagram corresponding to this panel. Middle, PNU-142633 (10 μM, 10 min), a specific 5-HT1D agonist, did not alter oEPSC amplitude (two-tailed paired Student’s t-test, t5 = 0.33, p = 0.76, n = 6 neurons from 3 animals). Bottom, representative oEPSC events during baseline after exposure to PNU-142633 (10 μM). Scale bars are 25 ms (horizontal) by 200 pA (vertical) for D, H, and I–K bottom. All error bars represent SEM. Source data are provided as a Source Data file.

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