Fig. 3: PVT→NAc-dependent suppression of sucrose seeking requires downstream CP-AMPArs and PV interneurons.
From: An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice
a Surgery for slice electrophysiology. b Example fluorescent images (left) and current-clamp traces (right) for NAc cell types (scale: 25 mV/0.2 s). c, d Example waveforms (c; pie charts show proportion of light-responding neurons) and grouped data (d) reveal elevated oeEPSC amplitudes in NAc PV-INs (D1-MSNs: n = 19 cells, 8 mice; D2-MSNs: n = 28 cells, 11 mice; PV-INs: n = 25 cells, 9 mice; one-way ANOVA, F2,69 = 27.78, P < 0.001; Sidak’s post-hoc: PV-INs vs D1/D2-MSNs P-values < 0.001). e, f Example waveforms (e) and grouped data (f) showing PVT→NAcPV-IN synapses are selectively inwardly rectifying (D1-MSNs: n = 11 cells, 5 mice; D2-MSNs: n = 10 cells, 5 mice; PV-INs: n = 16 cells, 7 mice). Inset: rectification index (I50/-I−70; one-way ANOVA, F2,34 = 13.27, P < 0.001; Sidak’s post-hoc: PV-INs vs D1/D2-MSNs P-values < 0.003). g, h Waveforms (g) and grouped data (h) showing that bath application of the CP-AMPAr antagonist IEM-1640 selectively reduced oeEPSC amplitudes at PVT→NAcPV-IN synapses (D1-MSNs: n = 7 cells, 5 mice; D2-MSNs: n = 5 cells, 4 mice; PV-INs: n = 10 cells, 5 mice; two-way ANOVA, cell type × time: F2,19 = 13.17, P = 0.003; Sidak’s post-hoc: PV-INs P < 0.001). i Surgery for simultaneous optogenetic manipulation of PVT→NAc neurons and intra-NAc neuropharmacology. j Microinfusions of the CP-AMPAr antagonist prevented the suppression of sucrose self-administration caused by stimulation of PVT→NAc neurons (n = 7 mice/group; two-way ANOVA, group × day: F3,24 = 5.98, P = 0.003; Sidak’s post-hoc: P-values < 0.01). k Surgery for simultaneous optogenetic stimulation of PVT→NAc neurons and chemogenetic inhibition of PV-INs. l CNO-mediated inhibition of NAc PV-INs prevented the suppression of sucrose self-administration caused by optogenetic stimulation of PVT→NAc neurons (n = 8 mice/group; two-way ANOVA, group x day: F2,28 = 11.33, P < 0.001; Sidak’s post-hoc: Opto + CNO P = 0.004). m–o Chemogenetic inhibition of PV-INs also prevented the suppression of sucrose self-administration caused by TMT (m), yohimbine (n), and extinction learning (o) (TMT: n = 8 mice/group; two-way ANOVA, group × day: F1,14 = 5.34, P = 0.04; Sidak’s post-hoc: TMT + CNO P = 0.002; yohimbine: n = 8 mice/group; ANOVA, group: F1,14 = 10.93, P = 0.01; Sidak’s post-hoc: yohimbine + CNO P = 0.005; extinction: n = 7 mice/group; ANOVA, group × day: F1,12 = 29.91, P = 0.001; Sidak’s post-hoc: extinction + CNO P < 0.001). CP-AMPAr calcium-permeable AMPA receptor, oeEPSC optically evoked excitatory postsynaptic current, SA self-administration, WT wild-type, Yoh yohimbine; Group comparisons: *P < 0.05, **P < 0.01, ****P < 0.001. Bar and line graphs are presented as mean ± SEM. Source data are provided as a Source Data file.
