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. 2023 Sep 14;26(10):107918. doi: 10.1016/j.isci.2023.107918

Figure 1.

Figure 1

Transient activation of TNSST neurons increased food intake across sexes

(A) Schematic of experimental paradigm. AAVs encoding hM3Dq-mCherry or GFP within flip-excision (FLEX) cassettes were injected bilaterally into the lateral tuberal nucleus (TN) of Sst-Cre or wild-type mice. Created with BioRender.com.

(B) Composite schematic of hM3Dq-mCherry expression.

(C) Fluorescent images of mCherry (magenta) and cFOS (yellow) in the TN of Sst-Cre mice and quantification of cFOS+ cells in these TN 90 min after CNO injection. Mice infected with h3MDq show an increase of cFOS-positive cells 90 min after CNO injection regardless of animal sex (overall effect of hM3Dq-mCherry presence, F(1,21) = 73.634, p < 0.0001; no interaction effect, F(1,21) = 0.939, p = 0.3435). Dashed ovals indicate boundaries of the TN. Scale bar = 100 μm.

(D) Activation of TNSST neurons in both female and male mice leads to higher food intake within the 4-h daytime testing period (left column, interaction between hM3Dq-mCherry presence and treatment: F(2,105) = 3.2964, p = 0.0409). Within sex, only males exhibited an effect of activation and treatment over time (F(2,45) = 3.2793, p = 0.0468), though both females and males exhibited an effect of hM3Dq presence and treatment independent of time (F(1,60) = 12.7928, p = 0.0007 and F(1,45) = 25.1794, p < 0.0001, respectively). Males also exhibited a significant hM3Dq-by-treatment interaction at 2 h post-CNO (F(1,9) = 8.69, p = 0.0163). CNO did not affect food intake in wild-type control mice (right column). Mean ± SEM; ANOVA and post hoc t tests where applicable ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001. F Control n = 6; M Control n = 5, F hM3Dq n = 8; M hM3Dq n = 6.