Article Figures & Data
Figures
- Figure 1.
Decreased quantity of parvalbumin-immunoreactive neurons in mPFC and CA1 during adolescence and adulthood in MAM-exposed mice. A, Schematic diagram of the immunofluorescence experimental procedure for staining PV neurons. B, Representative images of PV neurons in the mPFC, dCA1, and vCA1 of saline- and MAM (10 and 15 mg/kg)-exposed mice during adolescence. Scale bar, 100 μm. C–E, Number of PV neurons in the mPFC (C), dCA1 (D), and vCA1 (E) of saline- and MAM (10 and 15 mg/kg)-exposed mice during adolescence, respectively. F, Representative images of PV neurons in the mPFC, dCA1, and vCA1 of saline- and MAM (10 and 15 mg/kg)-exposed mice during adulthood. Scale bar, 100 μm. G–I, Number of PV neurons in the mPFC (G), dCA1 (H), and vCA1 (I) of saline- and MAM (10 and 15 mg/kg)-exposed mice during adulthood, respectively. N = 6 mice per group. Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Figure contributions: Z.H. and Q.H. performed the experiments and analyzed the data; Y.L. and J.X. assisted in the data analysis. See Extended Data Figures 1-1 and 1-2 for more details.
- Figure 2.
Impaired inhibition in mPFC of MAM-exposed mice. A, Schematic diagram of whole-cell patch-clamp recording in mPFC during adolescence. B, Representative traces of sIPSCs in mPFC pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adolescence. Calibration, 400 ms, 20 pA. C, D, Cumulative distribution of sIPSC interevent intervals (C) and average frequencies (D). E, F, Cumulative distribution of sIPSC amplitudes (E) and average amplitudes (F). N = 10, 9, and 7 cells from 3 to 4 mice per group, respectively. G, Schematic diagram of whole-cell patch-clamp recording in the mPFC during adulthood. H, Representative traces of sIPSCs in mPFC pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adulthood. Calibration, 400 ms, 20 pA. I, J, Cumulative distribution of sIPSC interevent intervals (I) and average frequencies (J). K, L, Cumulative distribution of sIPSC amplitudes (K) and average amplitudes (L). N = 9, 13, and 10 cells from 3 mice per group, respectively. Data are mean ± SEM. *p < 0.05, ***p < 0.001. Figure contributions: Q.H. performed the experiments and analyzed the data.
- Figure 3.
Impaired inhibition in dCA1 of MAM-exposed mice. A, Schematic diagram of whole-cell patch-clamp recording in dCA1 during adolescence. B, Representative traces of sIPSCs in dCA1 pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adolescence. Calibration, 400 ms, 20 pA. C, D, Cumulative distribution of sIPSC interevent intervals (C) and average frequencies (D). E, F, Cumulative distribution of sIPSC amplitudes (E) and average amplitudes (F). N = 11, 9, and 8 cells from 3 mice per group, respectively. G, Schematic diagram of whole-cell patch-clamp recording in dCA1 during adulthood. H, Representative traces of sIPSCs in dCA1 pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adulthood. Calibration, 400 ms, 20 pA. I, J, Cumulative distribution of sIPSC interevent intervals (I) and average frequencies (J). K, L, Cumulative distribution of sIPSC amplitudes (K) and average amplitudes (L). N = 10, 10, and 12 cells from 3 to 4 mice per group, respectively. Data are mean ± SEM. **p < 0.01, ***p < 0.001. Figure contributions: Z.H. performed the experiments and analyzed the data.
- Figure 4.
Impaired inhibition in vCA1 of MAM-exposed mice. A, Schematic diagram of whole-cell patch-clamp recording in vCA1 during adolescence. B, Representative traces of sIPSCs in vCA1 pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adolescence. Calibration, 400 ms, 20 pA. C, D, Cumulative distribution of sIPSC interevent intervals (C) and average frequencies (D). E, F, Cumulative distribution of sIPSC amplitudes (E) and average amplitudes (F). N = 14, 14, and 13 cells from 4 mice per group, respectively. G, Schematic diagram of whole-cell patch-clamp recording in vCA1 during adulthood. H, Representative traces of sIPSCs in vCA1 pyramidal neurons from saline- and MAM (10 and 15 mg/kg)-exposed mice during adulthood. Calibration, 400 ms, 20 pA. I, J, Cumulative distribution of sIPSC interevent intervals (I) and average frequencies (J). K, L, Cumulative distribution of sIPSC amplitudes (K) and average amplitudes (L). N = 14, 16, and 15 cells from 3 to 5 mice per group, respectively. Data are mean ± SEM. *p < 0.05, ***p < 0.001. Figure contributions: Z.H. performed the experiments and analyzed the data.
- Figure 5.
Abnormal spike firing of putative pyramidal neurons and putative inhibitory neurons in mPFC of MAM-exposed mice. A, Schematic diagram of in vivo electrophysiological recordings. B, Schematic representation of the multichannel electrodes implanted in the mPFC. C, Nissl staining plot of electrodes implanted in the mPFC. Scale bars: 1 mm (left), 250 μm (right). D1, Illustration of mPFC putative pyramidal neurons and putative inhibitory neurons firing spikes during adolescence. Scale bar, 60 s. D2, D3, Quantification of mean firing rate of mPFC putative pyramidal neurons (D2) and putative inhibitory neurons (D3). E1, Illustration of mPFC putative pyramidal neurons and putative inhibitory neurons firing spikes during adulthood. Scale bar, 60 s. E2, E3, Quantification of mean firing rate of mPFC putative pyramidal neurons (E2) and putative inhibitory neurons (E3). Each scatter represents a signal unit from 3 to 5 mice per group. Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Figure contributions: X.T. performed the experiments and analyzed the data.
- Figure 6.
Abnormal spike firing of putative pyramidal neurons and putative inhibitory neurons in vCA1 of MAM-exposed mice. A, Schematic representation of the multichannel electrodes implanted in the vCA1. B, Nissl staining plot of electrodes implanted in the vCA1. Scale bars: 1 mm (left), 250 μm (right). C1, Illustration of vCA1 putative pyramidal neurons and putative inhibitory neurons firing spikes during adolescence. Scale bar, 60 s. C2, C3, Quantification of mean firing rate of vCA1 putative pyramidal neurons (C2) and putative inhibitory neurons (C3). D1, Illustration of vCA1 putative pyramidal neurons and putative inhibitory neurons firing spikes during adulthood. Scale bar, 60 s. D2, D3, Quantification of mean firing rate of vCA1 putative pyramidal neurons (D2) and putative inhibitory neurons (D3). Each scatter represents a signal unit from 3 to 5 mice per group. Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. Figure contributions: X.T. performed the experiments and analyzed the data.
Extended Data
Figure 1-1
10 mg/kg and 15 mg/kg MAM-exposed mice exhibited schizophrenia-like behaviors during adolescence. A, Schematic representation of Saline- and MAM (10 mg/kg and 15 mg/kg)- exposed mice undergoing a series of schizophrenia-related behavioral tests during adolescence. B-D, MAM exposure induced locomotor hyperactivity in the open field test. Representative activity tracking (B), total distance (C) and time in center (D) [(C) F(2,22) = 7.616, p = 0.0031; (D) F(2,22) = 0.852, p = 0.4400]. E, F, No changes in social activity were observed. Representative activity tracking (E) and social preference indexes (F) in three-chambers social test [F(2,22) = 3.207, p = 0.0599]. G, No changes in alternation (%) in Y maze test [F(2,22) = 0.953, p = 0.4011]. H, I, MAM exposure induced an impaired PPI. Quantification of response to 70 dB (E) and percentage of PPI (F) in prepulse inhibition test [(E) p = 0.2761; (F) Two-way ANOVA, interaction: F(4, 66) = 0.323, p = 0.8619; main effect of decibel: F(2, 66) = 11.230, p < 0.0001; main effect of group: F(2, 66) = 19.120, p < 0.0001]. N = 8, 9, 8 mice per group. Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. Figure Contributions: Zhiyin He and Keni Huang performed the experiments and analyzed the data. Download Figure 1-1, TIF file.
Figure 1-2
10 mg/kg and 15 mg/kg MAM-exposed mice exhibited schizophrenia-like behaviors during adulthood. A, Schematic representation of Saline- and MAM (10 mg/kg and 15 mg/kg)- exposed mice undergoing a series of schizophrenia-related behavioral tests during adolescence. B-D, MAM exposure induced locomotor hyperactivity in the open field test. Representative activity tracking (B), total distance (C) and time in center (D) [(C) F(2,25) = 6.897, p = 0.0041; (D) F(2,25) = 0.122, p = 0.8858]. E, F, No changes in social activity were observed. Representative activity tracking (E) and social preference indexes (F) in three-chambers social test [F(2,25) = 0.200, p = 0.8201]. G, No changes in alternation (%) in Y maze test [F(2,25) = 0.394, p = 0.6787]. H, I, MAM exposure induced an impaired PPI. Quantification of response to 70 dB (E) and percentage of PPI (F) in prepulse inhibition test [(E) p = 0.7745; (F) Two-way ANOVA, interaction: F(4, 75) = 0.575, p = 0.6820; main effect of decibel: F(2, 75) = 64.010, p < 0.0001; main effect of group: F(2, 75) = 18.370, p < 0.0001]. N = 10, 9, 9 mice per group. Data are mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. Figure Contributions: Zhiyin He and Qian He performed the experiments and analyzed the data. Download Figure 1-2, TIF file.
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