Article Figures & Data
Figures
- Figure 1.
Summary of combined behavioral testing and stimulus-evoked LFP recordings in a latent inhibition paradigm. Rats were divided into two groups, with one group pre-exposed to a nonsalient tone and the other group having no tone presentation. All rats were subsequently exposed to a standard auditory fear conditioning procedure that involved a tone presentation that coterminated for the final second with a mild footshock. Twenty-four hours after conditioning, rats were placed in the conditioning chamber where the locomotor and tone-evoked responses to the conditioned tone were recorded.
- Figure 2.
Histological localization of electrode sites within the prefrontal cortex and hippocampus. Numbers beside each plate represent approximate A/P distance from bregma.
- Figure 3.
MAM-treated rats display a regionally specific reduction in the density of parvalbumin-positive neurons throughout the mPFC and the ventral vSub. Confocal z-stack images of parvalbumin- (red) and GAD67- (green) stained sections throughout the prelimbic subregion of mPFC (A) and vSub (B) demonstrate a decrease in PV interneurons. The density of parvalbumin and GAD-67-positive/parvalbumin-negative neurons are depicted in C and D, respectively. *Statistically significant difference from control (prenatal saline administration) (p < 0.05, one-way ANOVA, Tukey post hoc, n = 4–5 rats/group). Scale bars, 50 μm.
- Figure 4.
Spontaneous local field potential oscillations throughout the ventral hippocampus of saline- (A, B) and MAM- (C, D) treated rats. A time-domain reconstruction (A, C) demonstrates the predominant theta rhythm (blue line), a hallmark of oscillatory hippocampal activity, overlaid on a 2 s epoch of spontaneous activity (red line). The arrows indicate periods of high-frequency oscillations “riding” the theta wave. A continuous wavelet time-frequency spectrum (B, D) demonstrates the power (TISA), indicated by the red gradient contour, across frequency for a 4 min period (y1 axis). The global wavelet spectrum for the entire time range is depicted by the yellow line, plotted against the y2 axis.
- Figure 5.
Spontaneous local field potential oscillations throughout the medial prefrontal cortex of saline-(A, B) and MAM- (C, D) treated rats. A time-domain reconstruction (A, C) demonstrates a low-frequency (delta) rhythm (blue line) overlaid on a 2 s epoch of spontaneous activity (red line). Strong periodic high-frequency oscillations (∼20 Hz) are present in the raw trace. A continuous wavelet time-frequency spectrum (B, D) demonstrates the power (TISA), indicated by the red gradient contour, across frequency for a 4 min period (y1 axis). The global wavelet spectrum for the entire time range is depicted by the yellow line, plotted against the y2 axis.
- Figure 6.
MAM-treated rats display deficits in latent inhibition. Rats that had received a mild footshock paired with a tone display a robust decrease in locomotor activity in response to the conditioned tone (dark bars). Control rats (A) that had been exposed to the tone before the conditioning period displayed robust latent inhibition, i.e., an attenuated locomotor response to the tone (A, light bars). In contrast, MAM-treated rats (B) display a deficit in latent inhibition with the previous exposure to the tone having no significant effect on the locomotor response to the conditioned stimulus (B, light bars). *Significant difference compared with baseline; †significant difference between tone and no tone pre-exposure (p < 0.05, two-way RM ANOVA with Holm–Sidak post hoc: n = 5 rats/group).
- Figure 7.
mPFC theta response to the conditioned tone is reduced in MAM-treated rats. Multitaper spectral analyses of tone-evoked local field potential responses demonstrate that tone presentation alone induces a mild increase in prefrontal theta (4–12 Hz) oscillations in both saline (A) and MAM (B) rats. Control rats that had received a mild footshock paired with a tone display a massive and sustained increase in theta activity evoked by the conditioned tone (C), that is attenuated in rats that had been exposed to the tone before the conditioning period (E). In contrast, MAM-treated rats did not display a robust response to the conditioned tone either in rats with (F) or without (D) previous tone exposure. The horizontal line depicts the 2 s tone presentation whereas the dashed line represents the control response (i.e., no tone presentation); n = 3–5 rats/group.
- Figure 8.
vHipp theta is unaltered after fear conditioning. Multitaper spectral analyses of tone-evoked local field potential responses demonstrate that tone presentation alone has no significant effect on hippocampal theta (4–12 Hz) oscillations in saline (A) and MAM (B) rats. Interestingly, there were no significant changes in theta activity to the conditioned tone in either control rats (C, E) or MAM-treated rats (D, F). The horizontal line depicts the 2 s tone presentation, whereas the dashed line represents the control response (i.e., no tone presentation); n = 3–5 rats/group.
- Figure 9.
High-frequency mPFC responses to the conditioned tone are reduced in MAM-treated rats. Multitaper spectral analyses of tone-evoked local field potential responses demonstrate that tone presentation alone induces a mild increase in prefrontal gamma (30–55 Hz) oscillations in saline (A), but not MAM (B), rats. Control rats that had received a mild footshock paired with a tone display a transient but significant increase in high-frequency activity evoked by the conditioned tone (C), that is attenuated in rats that had been exposed to the tone before the conditioning period (E). In contrast, MAM-treated rats did not display a robust response to the conditioned tone either in rats with (F) or without (D) previous tone exposure. The horizontal line depicts the 2 s tone presentation whereas the dashed line represents the control response (i.e., no tone presentation); n = 3–5 rats/group.
- Figure 10.
The high-frequency responses to the conditioned tone are blunted in the vHipp of MAM-treated rats. Multitaper spectral analyses of tone-evoked local field potential responses demonstrate that tone presentation alone induces a mild increase in hippocampal gamma (30–55 Hz) oscillations in both saline (A) and MAM (B) rats. In contrast to that observed in the mPFC, neither saline nor MAM-treated rats displayed a robust response to the conditioned tone either in rats with (E, F) or without (C, D) previous tone exposure. However, a significant reduction in tone-evoked oscillatory activity was observed in MAM-treated rats. The horizontal line depicts the 2 s tone presentation whereas the dashed line represents the control response (i.e., no tone presentation); n = 3–5 rats/group).
- Figure 11.
MAM-treated rats display a significantly attenuated oscillatory activity during latent inhibition training and testing. Analysis of the maximum increase in oscillatory activity demonstrates significant deficits in the induction of mPFC theta (A) (4–12 Hz), mPFC gamma (C) (30–55 Hz), vHipp gamma (D) (30–55 Hz), but not vHipp theta (B) (4–12 Hz) between saline and MAM-treated rats. *Significant difference compared with no tone trials; ‡significant difference between tone (dark gray bar) and no tone (light gray bar) pre-exposure; †significant difference between saline and MAM-treated rats (p < 0.05, two-way ANOVA with Holm–Sidak post hoc: n = 3–5 rats/group).
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Supplemental Data
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