Fig. 1: Chemogenetic activation of VMH SF1 neurons inhibits food intake. | Nature Communications

Fig. 1: Chemogenetic activation of VMH SF1 neurons inhibits food intake.

From: An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake

Fig. 1

a Schematic illustration of co-transduction of VMH SF1 neurons with DREADDs and GCaMP6f protein and an optic fiber for photometry monitoring of VMH neurons. b Illustration of light pathways of fiber photometry. c A representative confocal image of hM3Dq-mCherry and GCaMP6f-transduced SF1 neurons and the optic fiber track. d (top) Two representative traces of real-time monitor of SF1 neuron GCaMP6f signals from the same mouse in the early light period (ELP) and late light period (LLP), respectively; (bottom) average intensity of basal GCaMP6f signal (0–15 min) was higher in the ELP than in the LLP (p = 0.0063, two-tailed Student’s t-test) and the amount of food intake was in opposite direction (p < 0.0001, two-tailed Student’s t-test) (n = 4 male and 4 female); 2-h food intake was measured in the ELP and LLP accordingly. e–h GCaMP6f signals were recorded in SF1 neurons transduced with DREADDs and GCaMP6f proteins: e J60 i.p. injections potently increased GCaMP6f signals in SF1 neuron hM3Dq-transduced mice (n = 5 males and 5 females) as compared to f vehicle injections (n = 6); g J60 i.p. injections decreased GCaMP6f signals in the VMH SF1 neuron hM4Di-transduced mice (n = 6) as compared to h vehicle treatment (n =6). i–l Food intake was evaluated in SF1-Cre mice transduced with DREADDs or mCherry: J60 i.p. injections significantly decreased food intake in the SF1 neuron i hM3Dq-transduced mice (n = 7 males and 7 females; p = 0.0001; two-way ANOVA with Sidak post hoc tests) but increased feeding in the j hM4Di-transduced mice (n = 7 males and 7 females; p = 0.0285; two-way ANOVA with Sidak post hoc tests) as compared to control k mCherry transduced mice (n = 4 males and 4 females; p = 0.9492; two-way ANOVA with Sidak post hoc tests); l group data of calculated food intake by subtracting the average amount of food consumed 4 h following vehicle i.p. injections from the average amount of food consumed 4 h following J60 i.p. injections for each mouse tested (hM3Dq, n = 14; hM4Di, n = 14; mCherry, n = 8; p = 0.0212, one-way ANOVA with Turkey post hoc tests; hM3Dq vs hM4Di, p = 0.012, two-tailed Student’s t-test; hM3Dq vs mCherry, p = 0.0331, two-tailed Student’s t-test). Data represent mean ± s.e.m.; *p < 0.05; **p < 0.01; ***p < 0.001; ***p < 0.0001; n.s. not significant. D’Agostino-Pearson normality tests were performed using column statistics, p = 0.20 and p = 0.18 for males and females, respectively; male and female homoscedasticity tests were performed using F-test, p = 0.96. Scale bar, 200 μm for c. ARC arcuate nucleus, DMH dorsomedial hypothalamus, ME medium eminence, PVT paraventricular thalamus, VMH ventromedial hypothalamus. Arrows point at the i.p. injection sites in e–h.

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