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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. 5. Activation of SuM circuit-modified adult-born neurons further improves memory performance.

Fig. 5

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

(b–c) Sample images showing expression (b) and density (c) of mCitrine+ hM3Dq cells in the DG in AAV-mCherry or AAV-ChR2 injected Ascl1-hM3Dq mice after optogenetic stimulation. Scale bar = 100 µm. n = 8 mice for mCherry group, n = 9 mice for ChR2 group, P = 0.0006 by two-sided unpaired t-test.

(d–e) Sample images showing expression (d) and density (e) of HA-tag+ hM4Di cells in the DG in AAV-mCherry or AAV-ChR2 injected Ascl1-hM4Di mice after optogenetic inhibition. Scale bar = 100 µm. n = 8 mice in each group, P = 0.0184 by two-sided unpaired t-test.

(f) Chemogenetic activation of circuit-modified newborn neurons further enhanced the discrimination ratio in the NPR test. n = 8 mice for mCherry group, n = 9 mice for ChR2 group. P = 0.0438 by two-sided unpaired t-test.

(g–j) Freezing time in context-A at 2 h (g), 24 h (h), in context-B at 24 h (i), and in context-A at 7 day (j) after chemogenetic activation of SuM circuit-modified or unmodified newborn neurons. n = 8 mice for mCherry group, n = 9 mice for ChR2 group, two-sided unpaired t-test, h: P = 0.8273, i: P = 0.0228, j: P = 0.1812, k: P = 0.0255, respectively.

(k) Chemogenetic inhibition of circuit-modified newborn neurons did not change the discrimination ratio in the NPR test. n = 8 mice for each group, P = 0.4615 by two-sided unpaired t-test.

(l–o) Freezing time in context-A at 2 h (l), 24 h (m), in context-B at 24 h (n), and in context-A at 7 day (o) after chemogenetic inhibition of SuM circuit-modified and unmodified newborn neurons. n = 8 mice for each group, two-sided unpaired t-test, l: P = 0.6585, m: P = 0.9374, n: P = 0.8168, o: P = 0.6433, respectively.