Fig. 5. Optogenetic stimulation of the LC-LHA noradrenergic pathway suppresses feeding, elicits aversion, and enhances anxiety-like behavior.
(A) Schematic illustration of sagittal mouse brain shows location of cre-dependent AAV used to drive ChR2-EYFP expression and location of fiber-optic probes. (B and C) Parasagittal brain section from a Dbhcre; LC-LHAEYFP mouse shows restricted EYFP expression in LC-NE neurons. High-magnification image shows EYFP-expressing LC-NE axonal projections in the LHA. Scale bars, 400 μm (brain) and 150 μm (LHA). (D) Timeline of FI during open-loop photostimulation (465 nm, 10 Hz, 10-ms pulses). (E and F) Average feeding-related behaviors measured in the presence (On) or absence (Off) of open-loop photostimulation in fasted mice. Two-way repeated-measures ANOVA, stimulation × virus interaction: food intake (E, left; F1,17 = 10.8, P = 0.0044) and ambulation (F; F1,18 = 0.655, P = 0.4290). Bonferroni post hoc test, *P < 0.05. Data are means ± SEM. n = 10 LC-LHAEYFP mice, n = 9 to 10 LC-LHAChR2 mice. Unpaired sample t test: food intake during photostimulation as a percent change from no photostimulation (E, right; t17 = 3.055, **P < 0.01). Data are means ± SEM. n = 10 LC-LHAEYFP mice and n = 9 LC-LHAChR2 mice. (G and H) OFT behaviors. Unpaired sample t test: center time (G; t17 = 2.279, *P < 0.05) and ambulation (H; t17 = 2.411, *P < 0.05). Data are means ± SEM. n = 10 LC-LHAEYFP mice and n = 9 LC-LHAChR2 mice. (I and J) EPM behaviors. Unpaired sample t test: open arm time (I; t17 = 1.638, P = 0.1199) and ambulation (J; t17 = 0.5101, P = 0.6165). Data are means ± SEM. n = 10 LC-LHAEYFP mice and n = 9 LC-LHAChR2 mice. (K and L) RTPT behaviors. Unpaired sample t test: stimulation side time (K; t12 = 2.498, *P < 0.05) and ambulation (L; t12 = 0.1369, P = 0.8934). Data are means ± SEM. n = 7 LC-LHAEYFP mice and n = 7 LC-LHAChR2 mice. (G, I, and K) Representative spatial location heatmaps show time spent exploring the arenas.