Fig 1.
Working memory impairment, which is not delay-dependent in chronic PCP-treated mice.
(A) Experimental schedules for the discrete paired-trial variable-delay task in T-maze and the drug treatments. (B) Schematic illustration of the forced alternation training sessions. (C) Significant decreases in latency to eat food pellets were observed over days during the forced alternation training with no group differences. (D) Schematic illustration of the discrete paired-trial delayed alternation training sessions. Before drug treatment, no group differences in days to reach criterion (E) and correct responses (F) were observed. (G) Schematic illustration of the variable delay test in T-maze. (H) Percent of correct responses by chronic saline- (n = 11 mice) and PCP-treated mice (n = 12 mice) for all variable delays (5, 15, and 30 sec). Note that the x-axis starts at 50%, the expected chance response accuracy. (I) No group differences in latency to reach the pellet cup during the variable delay test were observed. **p < 0.01, #p < 0.05; NS, no significance. Line graphs show mean ± standard error of the mean (SEM). Bar graphs show mean ± SEM.
Fig 2.
Quantification of c-Fos+ cells in the frontal cortex of chronic saline and PCP-treated mice.
(A) Schematic illustration of brain sampling schedule for brain-wide c-Fos mapping after working memory task. The timing of sampling for c-Fos immunohistochemistry is indicated with the red dashed lines. (B) Representative c-Fos staining (red) in the PL (B, top). Representative double staining for a layer 5 (and 6) marker, Ctip2 (magenta), and a layer 6 marker, Foxp2 (green), in sections adjacent to those used for c-Fos immunostaining in the PL (B, bottom). Scale bar, 100 μm. (C) Fluorescence microscopy images of c-Fos staining (red) in the frontal cortex of chronic saline- or PCP-treated mice. Scale bars, 100 μm. (D) Quantification of the total number of c-Fos+ cells in the ACC, PL, and IL of chronic saline- (0 min: n = 4, 90 min: n = 5) and PCP-treated mice (0 min: n = 4, 90 min: n = 5). (E–G) Quantitative laminar-specific c-Fos mapping in the ACC (E), PL (F) and IL (G). *p < 0.05, **p < 0.01, ***p < 0.001 vs 0 min, ##p < 0.01 vs saline (90 min). Graphs show mean + SEM.
Fig 3.
Quantification of c-Fos+ cells in the striatum of chronic saline- and PCP-treated mice.
Quantification of c-Fos+ cells in the DMS (A) and DLS (B) of chronic saline- (0 min: n = 4, 90 min: n = 5) and PCP-treated mice (0 min: n = 4, 90 min: n = 5). *p < 0.05, **p < 0.01 vs 0 min, #p < 0.05, ##p < 0.01 vs saline. Graphs show mean + SEM.
Fig 4.
Quantification of c-Fos+ cells in the thalamus of chronic saline and PCP-treated mice.
Quantification of c-Fos+ cells in the PVT, MD and RE of the thalamus of chronic saline- (0 min: n = 4, 90 min: n = 5) and PCP-treated mice (0 min: n = 4, 90 min: n = 5). ***p < 0.001 vs 0 min. Graphs show mean + SEM.
Fig 5.
Quantification of c-Fos+ cells in the hippocampus of chronic saline- and PCP-treated mice.
(A and B) Quantification of c-Fos+ cells in the DG, CA1, and CA3 of the dHPC (A) and vCA1/subiculum of the vHPC (B) of chronic saline- (0 min: n = 4, 90 min: n = 5) and PCP-treated mice (0 min: n = 4, 90 min: n = 5). **p < 0.01 vs 0 min, #p < 0.05 vs saline. Graphs show mean + SEM.
Fig 6.
Quantification of c-Fos+ cells and overlap of c-Fos and tyrosine hydroxylase immunoreactivities in the ventral tegmental area and substantia nigra of chronic saline- and PCP-treated mice.
(A) Representative full-focus images showing c-Fos and TH immunoreactivities in the VTA and SNC of chronic saline- and PCP-treated mice. Scale bar, 100 μm. (B and C) Quantification of c-Fos+ cells in the dSNC and mSNC of the SNC (B) and mVTA, lVTA and IF of the VTA of chronic saline- (0 min: n = 4, 90 min: n = 5) and PCP-treated mice (0 min: n = 4, 90 min: n = 5) (C). *p < 0.05, **p < 0.01 vs 0 min. Graphs show mean + SEM.