Fig. 5.

Optogenetic activation of the LHA^Orx-LHb^Glu circuit relieved anxiety-like behaviors after chronic social defeat stress

(a) Schematic diagram of virus injection and fiber implantation into the LHA (LHA^mCh represents the mCherry control group and LHA^ChR2 represents the optogenetic activation group) or the LHb (LHA^mCh-LHb represents the control group and LHA^ChR2-LHb represents the optogenetic activation group) of the Hcrt-cre mice. (b) Representative images of virus expression and optical fiber placement. (c) Representative trajectories of LHA^mCh and LHA^ChR2 mice in the elevated plus maze test. (d) Time spent in the open arms during optogenetic activation of LHA^mCh and LHA^ChR2 (16.41 ± 2.084 s vs. 120.8 ± 23.04 s, t = 4.511, p = 0.0007). (e) Time spent in the closed arms with optogenetic activation of LHA^mCh and LHA^ChR2 (232.0 ± 8.361 s vs. 113.7 ± 22.63 s, t = 4.906, p = 0.0002). (f) Number of entries into the open arms during optogenetic activation of LHA^mCh and LHA^ChR2 (3.286 ± 0.7781 vs. 8.714 ± 1.809, t = 2,757, p = 0.0174). (g) Representative trajectories of LHA^mCh-LHb and LHA^ChR2-LHb mice in the elevated plus maze test. (h) Time spent in the open arms with optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (20.19 ± 3.270 s vs. 71.49 ± 11.53 s, t = 4.280, p = 0.0011). (i) Time spent in the closed arms during optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (234.7 ± 7.556 s vs. 187.9 ± 14.60 s, t = 2.850, p = 0.0128). (j) Number of entries into the open arms during optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (3.429 ± 0.7190 vs. 14.14 ± 2.444, t = 4.206, p = 0.0012). (k) Representative trajectories of LHA^mCh and LHA^ChR2 mice in the open field test. (l) Total mobile time in the open field during optogenetic activation of LHA^mCh and LHA^ChR2 (69.90 ± 4.800 s vs. 113.4 ± 10.23 s, t = 3.592, p = 0.0058). (m) Time spent in the center zone of the open field during optogenetic activation of LHA^mCh and LHA^ChR2 (12.34 ± 0.7521 s vs. 21.97 ± 2.647 s, t = 3.204, p = 0.0108). (n) Number of line crossings in the open field during optogenetic activation of LHA^mCh and LHA^ChR2 (48.60 ± 5.810 vs. 100.5 ± 13.33, t = 3.319, p = 0.0090). (o) Representative trajectories of LHA^mCh-LHb and LHA^ChR2-LHb mice in the open field test. (p) Total mobile time in the open field during optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (72.20 ± 5.798 s vs. 131.9 ± 9.382 s, t = 5.136, p = 0.0006). (q) Time spent in the center zone of the open field during optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (12.70 ± 0.8678 s vs. 23.60 ± 1.438 s, t = 6.152, p = 0.0002). (r) Number of line crossings in the open field during optogenetic activation of LHA^mCh-LHb and LHA^ChR2-LHb (49.80 ± 4.420 vs. 104.5 ± 9.451, t = 4.891, p = 0.0009). Data are presented as the mean ± SEM. *p < 0.05, **p < 0.01 (unpaired t-test). LHA, lateral hypothalamic area; LHb, lateral habenula.