Fig. 2: Circuit-induced relapse requires dorsal hippocampal fear memory.

A Experimental design of adult male and female rats that were surgically implanted with cannulae aimed at the dorsal hippocampus (DH) and nucleus reuniens (RE). After recovery, animals were infused with vehicle (VEH) or the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), just prior to auditory fear conditioning (VEH, n = 19; APV, n = 18). After conditioning, animals underwent auditory CS extinction. After the last extinction session, animals received VEH or the γ-amino butyric acid (GABA)_A receptor agonist, muscimol (MUS), just prior to auditory extinction retrieval giving four groups (VEH-VEH, n = 10; APV-VEH, n = 10; VEH-MUS, n = 9; APV-MUS, n = 8). B Left panel displays percentage of freezing [mean ± standard error of the mean (SEM)] during the baseline (BL) and final conditioning CS. Middle panel displays percentage of freezing (mean ± SEM) during the first extinction block and the final extinction block. Right panel displays percentage of freezing (mean + SEM) with animals either receiving intra-RE VEH or MUS prior to extinction retrieval. Female animals are represented by white-filled and light orange-filled triangles, while male animals are represented by gray-filled and dark orange-filled diamonds in the bar graphs. *p < 0.05; **p < 0.01. C Representative location of the injector tip of the cannula tract in RE, top row, or DH, bottom row, of each animal included in the final analyses. Atlas figures are adapted from Swanson (2018).