Fig. 3: Fat- and sugar-responsive dHPC neurons control nutrient-specific preference.

a, Schematic of the two-bottle choice test in Fos^TRAP mice with selective ablation of nutrient-responsive dHPC neurons responding to IG infusion of sugar or fat. b, Representative images of nutrient-responsive HPC neurons from Fos^TRAP mice following IG infusion of sugar or fat, with or without caspase ablation. c,d, Quantification of tdTomato⁺ neurons in dHPC^Sugar mice with and without ablation (n = 11 for Sugar^Con, n = 7 for Sugar^Casp3, unpaired two-tailed t-test) (c) or dHPC^Fat mice with and without ablation (n = 9 for Fat^Con, n = 7 for Fat^Casp3, unpaired two-tailed t-test) (d). e–h, Two-bottle choice test intake of sugar and fat. e, Sugar licking in dHPC^Sugar mice with and without ablation (n = 9 mice per group, two-way ANOVA with Holm–Sidak post-hoc analysis). f, Fat licking in dHPC^Sugar mice with and without ablation (n = 8 for Fat^Con, n = 9 for Fat^Casp3, two-way ANOVA with Holm–Sidak post hoc analysis). g, Sugar licking in dHPC^Fat mice with and without ablation (n = 8 mice group, two-way ANOVA with Holm–Sidak post hoc analysis). h, Fat licking in dHPC^Fat mice with and without ablation (n = 8 mice per group, two-way ANOVA with Holm–Sidak post hoc analysis). i, Schematic of the Fos^TRAP approach to chemogenetically stimulate nutrient-responsive HPC neurons responding to IG infusion of sugar or fat. j, Representative images of dDG tdTomato⁺ neurons (magenta) and CNO-induced Fos expression (cyan) in dHPC^Sugar and dHPC^Fat mice. k–n, Effects of chemogenetic stimulation on sugar and fat consumption. k, Sugar licking in dHPC^Sugar mice with and without hM3Dq (n = 8 mice per group, two-way within-subjects ANOVA with Holm–Sidak post-hoc analysis). l, Fat licking in dHPC^Sugar mice with and without hM3Dq (n = 7 mice per group, two-way with-subjects ANOVA with Holm–Sidak post hoc analysis). m, Sugar licking in dHPC^Fat mice with and without hM3Dq (n = 7 mice per group, two-way within-subjects ANOVA with Holm–Sidak post hoc analysis). n, Fat licking in dHPC^Fat mice with and without hM3Dq (n = 6 mice per group, two-way within-subjects ANOVA with Holm–Sidak post hoc analysis). Data are presented as mean ± s.e.m. Images are representative of independent experiments from 7–11 (b) or 5–6 animals (j). Scale bars, 100 µm. Elements of a and i were created in Biorender.

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