Figure 1. Photostimulation of PVH^Mc4R→LSv fibers reduces feeding and induces aversion.

(A) Diagram depicting injections of the AAV-Felx-ChR2-eYFP virus to the PVH of MC4R-Cre mice.

(B) Viral expression pattern in PVH^Mc4R neurons within the PVH (left) and PVH^Mc4R→LSv fibers with c-Fos immunostaining (red) with photostimulation (middle) or without photostimulation (right).

(C) Food intake within 20 min after fasting with or without photostimulation at the indicated stimulation protocol (n = 8 mice; one-way ANOVA, **p < 0.01).

(D) Time spent in self-grooming during a 2-min period with photostimulation, 2 min immediately before and after photostimulation (n = 6 mice; one-way ANOVA, **p < 0.01).

(E–G) Mouse movement tracks in the place preference testing arena with half of the arena paired with photostimulation at 20 ms (E and F, n = 6 mice) and 100 ms (E and G) stimulation duration (n = 9 mice; paired t test, *p < 0.05, ***p < 0.001).

(H and I) Mouse movement tracks in the open-field arena with the peripheral area of the arena paired without photostimulation (H, left panel) or with photostimulation (H, right panel), and comparison of time spent in the central area between two conditions (I, n = 6 mice; paired t test, *p < 0.05).

(J and K) Movement tracks of fasted mice in the place preference testing arena with food placed in one corner of the half arena paired without photostimulation (J, left) or with photostimulation (J, right), and quantified comparisons of time spent in each zone (K, n = 6 mice for OFF and n = 8 mice for ON; paired t test, **p < 0.01, ***p< 0.001).

AcbSh, accumbens nucleus shell; LV, lateral ventricle; LSv, ventral lateral septum; PVH, paraventricular nucleus of hypothalamus; 3V, third ventricle. All data presented as mean ± SEM. Scale bars in (B) represent 100 μm in the right panel and 50 μm in the middle and left panels. See also Figures S1-S3.