Fig. 1: Inhibition of select PVT→NAc neuronal ensembles predicts sucrose self-administration and seeking.
From: An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice
a–c Behavioral design (a; image modified from Vollmer et al., 202171), schematic (b), and grouped data (c) for sucrose self-administration (n = 13 mice; two-way ANOVA, lever: F1,24 = 60.65, P < 0.001). d–f TMT (d), yohimbine (e), and extinction (f) suppressed lever pressing (n = 13 mice; TMT: two-tailed t-test t12 = 5.54, P = 0.001; yohimbine: t12 = 5.66, P = 0.001; extinction: t12 = 2.72, P = 0.02). g Cue presentation provoked reinstatement after extinction (n = 13 mice; t12 = 2.79, P = 0.02). h, i Surgery (h) for visualization of PVT→NAc neurons (i; top) and calcium-mediated fluorescent signals (i; bottom). j, k Averaged trace (j) and single-cell heatmap (k) revealing PVT→NAc dynamics during sucrose self-administration (n = 6 mice, 305 cells). l Clustering revealed three PVT→NAc neuronal ensembles during sucrose self-administration: excitatory (purple, 79 cells), non-responding (black, 153 cells), and inhibitory (green, 73 cells). m Active lever press decoding was most accurate for ensemble 3 during self-administration (two-way ANOVA, ensemble × shuffle interaction: F2,604 = 34.02, P < 0.001; Sidak’s post-hoc: Ps < 0.001). n, o Example waveforms (n) and grouped data (o) showing reduced PVT→NAc activity during self-administration but not a baseline (No-SA) session (n = 3–6 mice, 105–327 neurons; two-way ANOVA, session × time: F3,2116 = 5.19, P = 0.001; Sidak’s post-hoc: No-SA vs. other sessions, P-values < 0.002). p, q Grouped data (p) and heatmap (q) reveal within-session reductions in activity for each ensemble (two-way ANOVA, ensemble × time: F2,604 = 4.99, P = 0.007; Sidak’s post-hoc: excited vs. inhibited/non-responding, P-values < 0.001). r–t TMT (r), yohimbine (s), and extinction (t) prevented reductions in PVT→NAc activity (66–150 neurons/session; TMT: two-way ANOVA, session × time: F1,550 = 4.19, P = 0.04, Sidak’s post-hoc: P = 0.002; yohimbine: ANOVA, F1,274 = 12.59, P < 0.001, Sidak’s post-hoc: P < 0.001; extinction: ANOVA, session × time: F1,570 = 47.04, P < 0.001, Sidak’s post-hoc: P < 0.001). u PVT→NAc activity was reduced during cue-induced reinstatement (n = 124 cells; two-way ANOVA, session × time: F1,544 = 7.83, P = 0.005; Sidak’s post-hoc: P < 0.001). v, w Averaged trace (v) and heatmap (w) revealing PVT→NAc dynamics during cue reinstatement. x Clustering revealed three ensembles: excitatory (20 cells), non-responding (56 cells), and inhibitory (48 cells). y Active lever press decoding was most accurate for ensemble 3 during reinstatement (two-way ANOVA, ensemble × shuffle: F2,242 = 8.23, P = 0.0004; Sidak’s post-hoc: P < 0.001). z, aa Grouped data (z) and heatmap (aa) reveal reductions in activity for each ensemble during cue-induced reinstatement (two-way ANOVA, ensemble × time: F2,242 = 4.27, P = 0.015; Sidak’s post-hoc: non-responding vs. excited/inhibited, P-values < 0.004). FOV field of view, SA self-administration, Rein reinstatement, Yoh yohimbine. Group comparisons: *P < 0.05, **P < 0.01, ***P = 0.001, ****P < 0.001. Bar and line graphs presented as mean ± SEM. Source data are provided as a Source Data file.
