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. Author manuscript; available in PMC: 2022 Nov 6.
Published in final edited form as: Nat Neurosci. 2022 May 6;25(5):630–645. doi: 10.1038/s41593-022-01065-x

Fig. 6. Bidirectional manipulation of SuM circuit-modified adult-born neurons further modulates anxiety-like behavior.

Fig. 6

(a) Experimental protocol for chemogenetic activation or inhibition of adult-born neurons at 32 dpi during behavioral tests in Ascl1-hM3Dq or Ascl1-hM4Di mice.

(b–e) Chemogenetic activation of adult-born neurons reduces anxiety-like behavior, but not depressive-like behavior. Shown are the quantifications in open field test, including time spent in the center area (b) and total locomotion (c), time spent in open arms in zero maze test (d), and immobility time in forced swimming test (e). n = 14 mice in hM3 group, n = 11 mice in Ascl1-hM3 group, two-sided unpaired t-test, b: P = 0.0098, c: P = 0.8005, d: P = 0.0385, e: P = 0.6520, respectively.

(f–i) Chemogenetic inhibition of adult-born neurons promotes anxiety-like behavior, but not depressive-like behavior. Shown are the quantifications similar to (b–e). n = 8 mice in hM4 group, n = 9 mice in Ascl1-hM4 group, two-sided unpaired t-test, f: P = 0.0400, g: P = 0.0608, h: P = 0.0375, i: P = 0.6160, respectively.

(j) Experimental design for behavioral testing with chemogenetic activation or inhibition of adult-born neurons after optogenetic stimulation of SuM neurons for 32 days in Ascl1-hM3Dq or Ascl1-hM4Di mice.

(k–n) Chemogenetic activation of circuit-modified adult-born neurons by SuM stimulation further reduced anxiety-like behaviors. In open field test, time spent in the center area was increased after activation of SuM circuit-modified newborn neurons (k) in ChR2 mice, with no change in total locomotion (l). Activation of SuM circuit-modified adult-born neurons in ChR2 mice increased time spent in open arms in zero maze test (m) but did not change immobility time in forced swimming test (n). n = 8 mice for each group, two-sided unpaired t-test, k: P = 0.0144, l: P = 0.7478, m: P = 0.0249, n: P = 0.3287, respectively.

(o–r) Chemogenetic inhibition of circuit-modified adult-born neurons by SuM stimulation further regulated anxiety-like behaviors. Shown are the quantifications similar to (k–n). n = 8 mice for each group, two-sided unpaired t-test, o: P = 0.0424, p: P = 0.8075, q: P = 0.0421, r: P = 0.9910, respectively.