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. 2017 Dec 6;37(49):11967–11978. doi: 10.1523/JNEUROSCI.1668-17.2017

Figure 5.

Figure 5.

Reversal of anxiety- and depression-like phenotypes upon loss of Freud-1 in the absence of 5-HT1A autoreceptors. Tissues from mice with conditional KO of Freud-1 and 5-HT1A receptor in adult serotonin neurons (F1/1A dKO) were compared with 5-HT1A conditional KO (1AKO) or WT littermates (WT/WT). A, Tamoxifen-induced recombination. Costaining for YFP and TPH in the DR. Recombination occurred exclusively in 5-HT cells; 92% of TPH+ cells were YFP+. Scale bar, 100 μm. B, Loss of 5-HT1A autoreceptors. Immunostaining for 5-HT1A and TPH showed significant loss of 5-HT1A immunostaining in TPH+ cells of cF1/1A dko mice. White arrows indicate the presence of 5-HT1A receptors in non-TPH+ cells in DR. Scale bar, 100 μm. C, 5-HT1A autoradiography. 5-HT1A receptor autoradiography using 125I-MPPI of representative midbrain sections from WT/WT and cF1/1A dko mice, including dorsal (DR) and median (MR) raphe (boxes) and hippocampal sections. DR and MR showed significant decreases in 5-HT1A autoreceptor binding: DR (unpaired two-tailed Student's t test, df = 4, t = 11.24, ***p < 0.001), MR (unpaired two-tailed Student's t test, df = 4, t = 5.235, ***p < 0.001). D–H, Behavioral studies were done in either WT or conditional KO for Freud-1 (F1) and/or 5-HT1A receptor (1A) in littermate mice. D, EPM. No change in anxiety-like behavior (open arm time) was observed. E, OF. No difference among groups was observed in time spent in the large center. F, NSF. The latency to feed was not altered. G, FST. Immobility duration was reduced in F1/1A dKO versus WT and 1AKO mice (one-way ANOVA genotype × genotype interaction, F(2,25) = 4.463, p = 0.0067; post hoc Tukey). *p < 0.05 versus WT. #p < 0.05 versus 1AKO. H, TS. Immobility time was reduced in F1/1AKO compared with WT or 1AKO (one-way ANOVA genotype × genotype interaction, F(2,29) = 6.998, p = 0.0033; post hoc Tukey). #p < 0.05 versus F1/1AKO. I, BBK test. No difference in 30 min activity in novel arena was observed. Data points represent individual mice, with mean ± SEM: WT, n = 10; F1WT/1AKO, n = 11; F1/1AKO, n = 11.