Fig 1.
T-817MA ameliorated PPI deficits in PDGFR-β KO mice.
(A) Acoustic startle amplitudes measured in trials without a prepulse. No significant differences were observed in the acoustic startle amplitudes among the four groups of mice. Values indicate the mean ± SE. (B) PPI (% inhibition) at five different prepulse intensities (70, 72, 74, 78, and 82 dB). Statistical results by three-way ANOVAs indicated significant main effects of genotype and treatment. Cont-DW, control mice with distilled water (DW); Cont-T817, control mice with T-817MA; KO-DW, PDGFR-β KO mice with DW; KO-T817, PDGFR-β KO mice with T-817MA.
Fig 2.
T-817MA ameliorated social interaction deficits in PDGFR-β KO mice.
(A, B) Durations of each social behavior are indicated. a, p<0.05; aa, p<0.01 (Bonferroni test); *, p<0.05 (main effect of genotype); #, p<0.05 (main effect of treatment).
Fig 3.
T-817MA ameliorated deficits of phase-locked gamma oscillations (peak-ITC, 26.4–67.1 Hz) in PDGFR-β KO mice.
(A) Examples of ITCs (Gamma ITC), non-averaged evoked potentials in one trial (Raw EP), non-averaged gamma-filtered evoked potentials (Gamma-filtered EP) and averaged evoke potentials (Averaged EP) in the four groups of mice. (B) Power spectral density of the auditory evoked potentials during 50 ms before (Pre, black line) and after (Post, red line) the tone onset in the Cont-DW mouse shown in A. (C) Changes in mean total gamma power (26.4–67.1 Hz) of the evoked potentials during 50 ms before (Pre-tone) and after (Post-tone) the tone onset in Cont-Dw (blue line), Cont-T817 (orange line), KO-DW (grey line) and KO-T817 (yellow line). (D) Time course of mean ITC between 26.4–67.1 Hz for the Cont-DW mouse shown in Aa. The arrow indicates peak-ITC. (E) Comparison of peak-ITC among the four groups. Peak-ITC was significantly lower in PDGFR-β KO mice administered with distilled water (KO-DW) compared to control mice administered with distilled water (Cont-DW) and PDGFR-β KO mice administered with T-817MA (KO-T817). a, p<0.05 (Bonferroni test).
Fig 4.
Comparison of peak-ITC (30.4–67.1 Hz) among the four groups.
Peak-ITC was significantly lower in PDGFR-β KO mice administered with distilled water (KO-DW) compared to control mice administered with distilled water (Cont-DW) and PDGFR-β KO mice administered with T-817MA (KO-T817). aa, p<0.01 (Bonferroni test).
Fig 5.
Photomicrographs of the medial prefrontal cortex (mPFC, A), CA3 subfield of the hippocampus (B), basolateral amygdala (BLA, C), and superior colliculus (SC, D) of the four groups of mice.
Number of parvalbumin-immunoreactive neurons was decreased in PDGFR-β KO mice (KO-DW). Scale bar = 100 μm.
Fig 6.
T-817MA ameliorated the decrease in density of parvalbumin-immunoreactive neurons in the mPFC (A), hippocampus (B), basolateral amygdala (BLA) (C), and superior colliculus (SC) (D) of PDGFR-β KO mice.
**, p<0.01 (main effect of genotype); #, p<0.05 (main effect of treatment); a, significant difference between Cont-DW and KO-T817 in the BLA (Bonferroni test, p<0.01); b, significant difference between Cont-DW (Bonferroni test, p<0.01) and KO-T817 (Bonferroni test, p<0.05) in the SC.
Fig 7.
Significant correlations among neurophysiological, immunohistological, and behavioral parameters.
(A) Significant correlation was observed between peak-ITC and parvalbumin-immunoreactive neuron density in the mPFC. (B-E) Significant relationships were observed between parvalbumin-immunoreactive neuron density in the mPFC and the duration of approaching (B), parvalbumin-immunoreactive neuron density in the mPFC and the duration of social sniffing (C), parvalbumin-immunoreactive neuron density in the mPFC and the duration of passive contact (D), parvalbumin-immunoreactive neuron density in the hippocampus (Hip) and the duration of approaching (E) (p<0.05). (F, G) Significant relationships were observed between parvalbumin-immunoreactive neuron density in the mPFC and % inhibition at 74 dB in the PPI test (F) and parvalbumin-immunoreactive neuron density in the hippocampus (Hip) and % inhibition at 74 dB in the PPI test (G) (p<0.05). Circles, Cont-DW; squares, Cont-T817; triangles, KO-DW; Crosses, KO-T817.