Fig. 3: Serpinb2⁺ neurons bidirectionally regulate food seeking and intake.

a, Experimental scheme of the food approach and food consumption assays. b, Heat map encoding the spatial location of a fasted mouse using the free-access feeding paradigm. c, Percentage of time that mice spent in the food zone. Chemogenetic activation (hM3Dq) or inhibition (hM4Di) of Serpinb2⁺ neurons (left), Tac2⁺ neurons (middle) and Drd1⁺ neurons (right). n = 8 mice per group. One-way ANOVA, F_2,21 = 15.05 (left), F_2,21 = 1.970 (middle), F_2,21 = 1.7 (right). d, Total food consumption during the 3 h test. Chemogenetic activation (hM3Dq) or inhibition (hM4Di) of Serpinb2⁺, Tac2⁺ and Drd1⁺ neurons. n = 8 mice per group. Two-tailed, unpaired t-test, t₁₄ = 0.5472 (Serpinb2-Cre, left), t₁₄ = 3.552 (Serpinb2-Cre, right), t₁₄ = 0.5472 (Tac2-Cre, left), t₁₄ = 1.703 (Tac2-Cre, right), t₁₄ = 0.278 (Drd1-Cre, left), t₁₄ = 0.4571 (Drd1-Cre, right). e, DO-EGFP/hM3Dq-EGFP virus expression in NAcSh and number of cFos⁺ neurons after CNO treatment. One technical replicate of three biological replicates. Two-tailed, unpaired t-test, t₄ = 20.84. Scale bars, 100 μm. f, Percentage of time that mice spent in the food zone. n = 8 mice per group. One-way ANOVA test, F_2,21 = 6.2. g, Total food consumption during the 3 h test. n = 8 mice per group. One-way ANOVA test, F_2,21 = 3.7. h, Illustration of the food operant chamber paradigm. Mice were trained to press the lever to get food; pressing the active lever is followed by the delivery of a food pellet; pressing the inactive lever yields no outcome. The behavioral training includes a habituation phase and a fixed ratio (FR) training phase. Mice received CNO injection (2 mg kg⁻¹ for the hM3Dq group and 5 mg kg⁻¹ for the hM4Di group) 15 min before they were placed into the operant chamber to start the FR and progressive ratio (PR) tests. i, Results of FR5 test. The total number of active lever presses (left) and total number of rewards (right) after chemogenetic manipulations. n = 15 mice for each group. One-way ANOVA test, F_2,42 = 15.20 (left), F_2,44 = 10.14 (right). j, Results of the PR5 test. The total number of active lever presses (left) and total number of rewards (right) after chemogenetic manipulations. n = 15 mice for each group. One-way ANOVA test, F_2,42 = 10.70 (left), F_2,44 = 21.19 (right). Data are represented as mean ± s.e.m. The graphics of the mouse and chamber in h were created with BioRender.com.

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