Fig. 1: Syt11 deficiency in dopamine neurons leads to schizophrenia-like behaviors. | Nature Communications

Fig. 1: Syt11 deficiency in dopamine neurons leads to schizophrenia-like behaviors.

From: Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission

Fig. 1

a, b Transcript expression levels of Syt11 in the dlPFC of postmortem brains from schizophrenia (SCZ) patients vs healthy controls (HC). RNA-sequencing data set were obtained from the Lieber Institute for Brain Development (LIBD), the CommonMind Consortium (CMC), and the Human Brain Collection Core (HBCC). The CMC and HBCC data sets were performed at a single facility with similar processes and thus combined to minimize site-specific sources of technical variation. c Transcript expression levels of Syt11 in peripheral blood from SCZ patients vs HC. d Representative western blots and expression levels of Syt11 in plasma from SCZ patients vs HC. e Transcript expression levels of Syt11 in peripheral blood from HC and SCZ patients before (SCZ-pre) and after (SCZ-post) antipsychotic treatment. f Changes in SCZ symptoms scores of SCZ patients after treatment with olanzapine, haloperidol, or risperidone. g Transcript expression changes of Syt11 in peripheral blood from SCZ patients after treatment with olanzapine, haloperidol, or risperidone. h Pearson correlation analysis between changes in Syt11 expression and changes in SCZ symptom scores after antipsychotic treatment as in (e-g). i Schematic of the generation of DA neuron-restricted Syt11 conditional knockout (cKO) mice. j Representative micrograph showing the immunostaining of Syt11 (red) and TH (green) in a VTA-containing slice (enlarged insets in the lower panel). Scale bars: 500 μm (upper), 100 μm (lower). Data from 3 mice. k, l Schematic, representative heat maps, and statistics of the three-chamber social interaction test of juvenile (6–8 weeks) Syt11-cKO or DAT-Cre (Ctrl) mice. M1, a novel mouse; F, fake toy mouse. Sniffing time and social index of Syt11-cKO vs control mice were used for analysis. m Schematic and representative heat maps of the three-chamber social novelty test of juvenile Syt11-cKO vs control mice. M1, familiar mouse (the former novel mouse in k and l); M2, new comer novel mouse. n, o Statistics of sniffing time (with M1 or M2) and total social time (sniffing with M1 and M2) of Syt11-cKO vs control mice. p Left, schematic and representative heat maps of the social approach test. Right, statistics of sniffing time with a caged novel mouse of Syt11-cKO vs control mice (6–8 weeks). q Statistics of sniffing time with an intruder mouse of Syt11-cKO vs control mice (6–8 weeks) in the home-cage social test. r, s Statistics of startle responses and pre-pulse inhibition (PPI) of juvenile (6–8 weeks) and adult (3-4 months) Syt11-cKO mice vs control mice. t Statistics of short-term memory (T-maze) of juvenile and adult Syt11-cKO mice vs control mice. u Statistics of the spontaneous alternation Y-maze test of juvenile and adult Syt11-cKO mice vs control mice. Data are shown as box-and-whisker plots, with the median represented by the central line inside each box, the 25th and 75th percentiles represented by the edges of the box, and the whiskers extending to the most extreme data points. Two-tailed Mann-Whitney test for (a-d, l, o-q, r-u), Pearson correlation analysis for (h), one-way ANOVA for (f, g), or Ordinary two-way ANOVA followed by Bonferroni’s multiple comparisons for (e, k, n), *P < 0.05, **P < 0.01, ***P < 0.001, n.s. no significant difference. Source data are provided as a Source Data file.

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