Fig. 3 | Molecular Psychiatry

Fig. 3

From: Emergence of 5-HT5A signaling in parvalbumin neurons mediates delayed antidepressant action

Fig. 3

5-HT5A signaling in PV neurons. a Bar graph summary of cAMP level in N2A cells transiently transfected with mouse 5-HT5A. The cells were incubated with the indicated amounts of forskolin and 5-HT. One representative experiment out of three is shown. Bars represent means of cAMP level (n = 4 wells per group) as percentage of baseline + SD. One Way ANOVA, *P < 0.05 vs. baseline. b Representative western blot images (top) and bar graph summary (bottom) depicting the levels of Kv3.1β and Ser503 pKv3.1β in transfected HEK293 cells treated as indicated (n = 4 wells per condition). Bars represent mean densities of the pKv normalized to that of the total Kv. Number and arrowhead indicate protein size in kDa. One-way ANOVA. *P < 0.05, **P < 0.01. OA okadaic acid, PMA Phorbol 12-myristate 13-acetate. c Representative traces of Kv potassium currents evoked with 10 mV potential steps from −70 to +50 mV in PV DG neurons from Veh- and Flx-treated WT mice. d PMA (200 nM) decreased the amplitude of KV currents in Flx-treated mice (n = 4, 3) but not Veh-treated WT mice (n = 3, 3). RM one-way ANOVA, *P < 0.05. e Model for serotonergic signaling in PV hippocampal cells. Left: initial exposure to SSRIs does not alter cAMP levels and PKA activity. PP2A activity remains high and Kv3.1β is dephosphorylated. Right: chronic SSRIs increases 5-HT5A surface levels. 5-HT5AR activation reduces cAMP levels and diminishes PKA and PP2A activities to reduce Ser 503 Kv3.1β dephosphorylation

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