Fig. 3: 5HT preferentially inhibits D1 MSNs that signal aggression.

a Experimental strategy: miniscope recording of either D1 or D2 MSNs expressing FLEX-GCaMP8m in the NAc after the mouse was injected with either saline or MDMA (7.5 mg/kg). b Change in the inferred spike rate in D1 MSNs after saline or MDMA injection. Grey areas indicate injection time (n = 8 D1-Cre mice). c Same as (b) but for D2 MSNs (n = 7 A2A-Cre mice). d Change in the average inferred spike rate in D1 and D2 MSNs post MDMA injection compared to baseline (**P = 0.0037, two-sided test Wilcoxon rank-sum test, n = 8 D1-Cre mice and 7 A2A-Cre mice). e D1-Cre or A2A-Cre mice were crossed with SERT-Flp mice to create double transgenic D1-Cre × SERT-Flp or A2A-Cre × SERT-Flp mice. f Double-transgenic mice in (e) were injected with Cre-dependent GCaMP8m virus in the NAc and Flp-dependent ChRimsonR in the DR. Schematic was adapted from ref. ¹⁰, Springer Nature. g Example brain slice showing the expression of GCaMP8m in NAc neurons and ChrimsonR in the terminals of 5HT neurons. Scale bars, 1 mm. h Validation experiment: SERT-Flp mice were injected with Flp-dependent ChRimsonR in the DR and GRAB-5HT in the NAc and an optical fiber was implanted in the NAc to record 5HT signals during photostimulation of 5HT terminals (n = 2 mice: 1 SERT-Flp × D1-Cre and 1 SERT-Flp × A2A-Cre). i Calcium activity of D1 MSNs aligned with photostimulation (30 s, 20 Hz, n = 6 D1-Cre × SERT-Flp mice). j Same as (i) but for D2 MSNs (n = 6 A2A-Cre × SERT-Flp mice). k Average calcium response to photostimulation in D1 and D2 MSNs (**P = 0.0022, two-sided Wilcoxon rank-sum test, n = 6 D1-Cre × SERT-Flp mice and 6 A2A-Cre × SERT-Flp mice). l Percentage of cells robustly activated or inhibited across trials (n.s. P = 0.41, 0.77, **P = 0.0030, ***P = 0.00073, two-way ANOVA followed by Tukey-Kramer test). m Calcium activity of aggression-modulated D1 MSNs around aggressive approach. Each row is a cell, sorted by the calcium response in time 0-2 s (n = 344 cells, 12 sessions, 6 mice). n Calcium activity of the same cells in (m) aligned with photostimulation, which was delivered after the aggression sessions while mice rested in their home cages. o Photostimulation response of cells sorted by aggression response as in (m, n). (top to bottom: ** P = 0.007, *P = 0.035, 0.031, n.s. P = 0.35, 0.84, two-sided one-sample t-test). Data are presented as mean values +/− SEM. Source data are provided as a Source Data file. ‘NAc’, nucleus accumbens; ‘DR’, dorsal raphe; ‘Fzsc’, zscored fluorescence; ‘Photostim.’, photostimulation; ‘n.s.’, not significant.