Fig. 3: CCC alterations in PTSD.

a, Barplot of the log differential output of all sender cell types. The SST IN was downregulated in its output signalling (log differential output = −0.518). b, Circos plot showing differential strength of all cell-to-cell interactions from SST INs between PTSD and CON. The shading indicates their quantitative values, with higher numbers indicating higher differential strengths. c, Mean SST log-normalized counts comparing 10 CON versus 4 PTSD samples by cell types. d, CON slide with SST transcripts indicated in dark green and each nucleus in its corresponding cell-type colour in a lighter shade (IN in light green). The CON inset zooms into layer 5, showing higher expression of SST in IN nuclei. One experiment was conducted. e, PTSD slide with SST transcripts indicated in dark green and each nucleus in its corresponding cell-type colour in a lighter shade (IN in light green). The PTSD inset zooms into layer 5, where SST expression is decreased. One experiment was conducted. f, Circos plots of GABA–GABRA5, GABA–GABBR1, GABA–GABRB1 and GABA–GABRG1 showing a decrease in differential output strength of all cell-to-cell interactions from SST INs in individuals with PTSD. Edges are coloured by interaction strength in PTSD cells (red denotes stronger, and blue indicates weaker). g, Schematic of the slice electrophysiology experimental setup. ChR2 was selectively expressed in SST IN in the mouse mPFC. IPSCs were evoked with 470-nm light pulses and recorded in mPFC layer 5 pyramidal neurons (Pyr). h, Representative eIPSCs (baseline in black, MRX 016 in red, and after washout in grey) recorded in control versus SPS mice i, Quantification of the percentage of IPSC amplitude change in the GABARα5 antagonist MRX 016 compared with baseline. Two-sided Student’s t-test was used, P = 0.01. n = 10 control samples and n = 18 SPS samples. Lines indicate mean, and error bars denote s.e.m. j, Schematic of the experimental setup. k, Representative traces from control (top) and SPS (bottom) held at 0 mV with Baclofen (a GABA_B receptor agonist) and washing in CGP 55845 (a GABA_B receptor antagonist). CGP 55845 induced a decrease in GABA tonic current in a pyramidal neuron in control but not in SPS. Red dotted lines indicate average baseline holding current before and after CGP 55845 bath application. l, Quantification of the size of GABA tonic current in control versus SPS. Two-sided Welch’s t-test was used, P = 0.02. n = 28 control samples and n = 22 SPS samples. Lines indicate mean, and error bars denote s.e.m. *P < 0.05.

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