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. 2019 Apr 29;8:e46348. doi: 10.7554/eLife.46348

Figure 1. NPY is uniquely required for sustained hunger driven by AgRP neurons.

(a) AgRP neurons are rapidly inhibited by food presentation but nevertheless promote food intake through a sustained hunger signal. (b) System for measuring food intake in response to activation of AgRP neurons in animals with blockade of signaling through AgRP, GABA or NPY (indicated as -) or littermate controls (indicated as +). (c) Raster plot showing pellet consumption of mice with different genotypes in response to pre-stimulation of AgRP neurons (15 min). Each row shows a representative trial from an individual mouse. (d) Feeding behavior paradigm with variable pre-stimulation lengths (blue). (e-g) Food intake (1 hr) following pre-stimulation of variable lengths. Genotypes: AgRP+ (black; N = 10) and AgRP- (red; N = 5) (e), GABA+ (black; N = 6) and GABA- (red; N = 8) (f), and NPY+ (black; N = 7) and NPY- (red; N = 6) (g). (h) Feeding behavior paradigm with variable delay length inserted between the end of pre-stimulation and start of food availability. (i-k) Food intake (1 hr) following pre-stimulation (5 min) and delay of varying lengths. Genotypes: AgRP+ (black; N = 6) and AgRP- (red; N = 6) (i), GABA+ (black; N = 5) and GABA- (red; N = 7) (j), and NPY+ (black; N = 7) and NPY- (red; N = 4) (k). (l) Image of ARC from NPY- mice that received laser stimulation (30 min) in the absence of food before perfusion. Sample was stained for ChR2-EYFP (cyan) and Fos (magenta). (m) Logarithmic growth model of relationship between food intake and pre-stimulation duration (N = 23 mice). (n) Exponential decay model of the relationship between food intake and delay length (N = 18 mice). Error bars in e-g, i-k, m and n represent mean ± SEM. Holm-Sidak multiple comparisons test was used to report adjusted P-values in e-g and i-k. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 or ns (not significant) compares adjacent control (black) and experimental (red) group with same pre-stimulation protocol.

Figure 1.

Figure 1—figure supplement 1. Temporal pattern of pellet consumption in response to different pre-stimulation protocols.

Figure 1—figure supplement 1.

(a–f) Raster plot of pellet intake (1 hr) by AgRP- (a), AgRP+ (d), GABA- (b), GABA+ (e), NPY- (c) and NPY+ (f) mice in response to pre-stimulation of variable length. Red color indicates cumulative food consumption at each time point. (g–l) Raster plot of pellet intake (1 hr) by AgRP- (g), AgRP+ (j), GABA- (h), GABA+ (k), NPY- (i) and NPY+ (l) mice in response to pre-stimulation (5 min) followed by a delay of variable length.

Figure 1—figure supplement 2. Bout analysis of food intake in response to pre-stimulation a-c.

Figure 1—figure supplement 2.

Bout size for food intake (1 hr) by AgRP+ (N = 10) and AgRP- (N = 5) (a), GABA+ (N = 6) and GABA- (N = 8) (b), and NPY+ (N = 7) and NPY- (N = 6) (c) mice in response to pre-stimulation of variable length. (d–f) Bout size for food intake (1 hr) by AgRP+ (N = 6) and AgRP- (N = 6) (d), GABA+ (N = 5) and GABA- (N = 7) (e), and NPY+ (N = 7) and NPY- (N = 4) (f) mice in response to pre-stimulation followed by a delay of variable length. (g–i) Bout number for food intake (1 hr) by AgRP+ (N = 10) and AgRP- (N = 5) (g), GABA+ (N = 6) and GABA- (N = 8) (h), and NPY+ (N = 7) and NPY- (N = 6) (i) mice in response to pre-stimulation of variable length. (j–l) Bout size for food intake (1 hr) by AgRP+ (N = 6) and AgRP- (N = 6) (j), GABA+ (N = 5) and GABA- (N = 7) (k), and NPY+ (N = 7) and NPY- (N = 4) (l) mice in response to pre-stimulation (5 min) followed by a delay of variable length.