Fig. 3: Distinct subpopulations of prelimbic cortex neurons respond to food cues during transitions between different metabolic or threat states.

a Left, schematic of microendoscopic imaging; Right, schematic of cue responses analysis: 1. Alignment of the calcium transients to food cue onsets; 2. Perievent activities of two representative neurons averaged across all trials and normalised to Z-score; 3. Permutation test results of two representative neurons. Grey bars showing null distribution of the Z-score difference between the 1.5-s pre-cue window and the 0.5-s post-cue window after 1000 random circular shifts of calcium traces. Coloured bars showing the real values. Red dotted lines showing the 2.5% and 97.5% of the null distribution. Left schematic created in BioRender. Zhang, X. (2025) https://BioRender.com/30ckzl8. b Representative traces of two cue-responsive neurons. c Trial-averaged perievent heatmap showing food-cue responses of neurons that are excited during hungry (left) and neurons that are inhibited by food cues during satiation (right). Trial-averaged food cue responses of all PL neurons during d hungry vs. satiated phase (n = 1111, from 19 animals) or j safe vs. threat phase (n = 938, from 14 animals). Trial-averaged food cue responses of neurons that are excited in e hungry states (n = 37) or satiated states (n = 41), and in k safe states (n = 28) or threat states (n = 23). Trial-averaged food cue responses of neurons inhibited in f hungry states (n = 31) or satiated states (n = 18) and l safe states (n = 27) or threat states (n = 11). g, m Left, Venn diagram showing the number of neurons that are exclusively responsive to food cues in each state or showing mixed responses to both states; Right, Representative distribution of responsive neurons in one animal. PL neurons that are preferentially recruited to respond to food cues in h hungry or i satiated states, and in n safe vs. o threat states. Inset of each panel: area under curve value during the 1.5 s post-cue window. f Two-sided unpaired Student’s t test; e, k, l, Two-sided Mann–Whitney U test; h left, i right, n, o right, Two-sided paired Student’s t test; d, h right, i left, j, o left, Two-sided Wilcoxon’s signed-rank test. Data in d–f, h–l, n–o shown as mean ± SEM, *p < 0.05. Box plot centre line, median; box limits, upper and lower quartiles; whiskers, 1.5× interquartile range; points, outliers. Source data are provided as a Source Data file.