Extended Data Fig. 11: Whole brain cFos expression in response to semaglutide, MK-801, GLP-1 and GLP-1–MK-801.
From: GLP-1-directed NMDA receptor antagonism for obesity treatment
a-j, Whole-brain 3D mapping and quantification of cFOS responses to treatment single s.c. injection with 100 nmol kg−1 MK-801 (n = 7 mice), 100 nmol kg−1 GLP-1 (n = 8 mice), 100 nmol kg−1 GLP-1–MK-801 (n = 7 mice) or vehicle (isotonic saline, n = 8 mice) in lean mice. One mouse in MK-801 group, GLP-1–MK-801 group and vehicle group were excluded from analysis due to sample processing related deviation. a, Schematic. b, Mouse brain images showing heatmap of averaged changes in cFOS expression in response to treatments relative to vehicle. Red areas indicate increased cFOS activity and blue areas indicate decreased cFOS activity. c, Heatmap of cFOS activity in brain regions involved in body weight regulation. Values exceeding the colour scale are presented with the numeric values. d, Volcano plot of brain regions regulated in response to MK-801 relative to vehicle. Selected regions are labelled. e, Volcano plot of brain regions regulated in response to GLP-1 relative to vehicle. Selected regions are labelled. f, Volcano plot of brain regions regulated in response to GLP-1–MK-801 relative to vehicle. Selected regions are labelled. g, Quantification of cFOS+ cells in dorsal motor nucleus X (DMX). h, Quantification of cFOS+ cells in nucleus of the solitary tract (NTS). i, Quantification of cFOS+ cells in rostral linear nucleus raphe (RR). j, Quantification of cFOS+ cells in Edinger-Westphal nucleus (EW). k-o, cFOS+ whole-brain imaging data came from mice in Fig. 5f–i. One mouse in GLP-1–MK-801 group excluded due to sample processing related deviation. k, cFOS+ cells in nucleus accumbens (NAc). l, cFOS+ cells in ventral tegmental area (VTA). m, cFOS+ cells in basolateral amygdala nucleus (BLA). n, cFOS+ cells in central amygdala (CEA). o, cFOS+ cells in agranular insular area (AI). Data analysed by one-way ANOVA, multiple comparison, Bonferroni post hoc test (g-o). Data analysed by one-way ANOVA, multiple comparison, Bonferroni post hoc test (g-o). Benjamini-Hochberg adjusted P (d-f). Data represents mean ± SEM; **P < 0.01, ***P < 0.001, ****P < 0.0001. For brain region abbreviations please refer to ‘cFos whole-brain imaging’ in the methods section. Detailed statistics are in Supplementary Table 1. The diagram in a was created using BioRender.