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. Author manuscript; available in PMC: 2023 Aug 1.
Published in final edited form as: Mol Psychiatry. 2022 Oct 12;28(2):611–624. doi: 10.1038/s41380-022-01820-3

Figure 4. Sex-specific effects of stress on PFC-BLA inhibitory control.

Figure 4.

(A, Top) A diagram illustrating the recording paradigm (see Supplementary Methods for details). A stimulating electrode and a recording electrode were implanted in the prelimbic prefrontal cortex (plPFC) and the BLA, respectively. BLA pyramidal neurons responsive to repeated plPFC single-pulse stimulation (0.5 Hz; 0.1-1.5 mA; square wave with 0.25ms duration) were searched and recorded for 10 minutes to obtain baseline measures (spike probability maintained at ~50%). High-frequency stimulation (HFS; 20 Hz; 10s, suprathreshold) was given immediately following the baseline recording, and spike probability response to HFS was recorded for an additional 30 minutes (Post-HFS). (A, Bottom) BLA pyramidal neurons typically respond to plPFC HFS with a long-term depression (LTD) of spiking, i.e., exhibiting fewer action potential responses to PFC stimuli after HFS. (B) Representative photomicrographs of plPFC stimulating electrode and BLA recording electrode placement. (C) In <3 weeks after stress, PreP-S induced a male-specific precocious form of PFC-BLA spike LTD in the first 10 minutes of post-HFS recordings (left), whereas in females PreP-S did not induce an effect (right) (time-course data). (D) No short-term effect of PreP-S was found across the test intervals in the mean Post-HFS spike probability change. (E) At >6 weeks after PreP-S, stressed rats (solid circles) of both sexes failed to show HFS-induced LTD (time-course data). (F) PreP-S induced impaired mean LTD averaged across test intervals in both sexes. (G) In <3 weeks post-stress, PostP-S induced a male-specific LTD impairment at 25-30 minutes post-HFS. (H) When averaged across the entire Post-HFS testing period, there was only a trend towards LTD impairment in males. (I) In >6 weeks post-stress, PostP-S induced a robust LTD deficit in the time course response only in males. (J) In >6 weeks post-stress, averaging across the entire test interval showed significant LTD impairments only in PostP-S males. Time-course data were analyzed by repeated measure two-way ANOVA with Bonferroni tests at each time point. Mean post-HFS response was analyzed by two-way ANOVA with Tukey’s post hoc test. *p<0.05; **p<0.01.