Fig. 2: Astrocytes bidirectionally modulate memory retrieval.

a, Combined in vivo Ca²⁺ fibre photometry and astrocyte hM3Dq actuation. b, hM3Dq-mCherry expression in astrocytes (GFAP) and neurons (NeuN) (two-tailed paired t-test, *P < 0.0001). n = 12 sections, n = 4 mice. Scale bars, 200 μm (left) and 10 μm (right). c, CNO effects on neutral-cage Ca²⁺ activity (two-tailed unpaired t-tests at minute 29, *P = 0.004). n = 7 (control) and n = 9 (hM3Dq) mice. d, Experimental timeline. e, CNO effects on CS-related freezing (two-way repeated-measures ANOVA, with Šídák’s or Fisher’s least significant difference (LSD) post hoc tests, control versus hM3Dq for Ext block 1 (*P < 0.0001), Ext block 2 (*P = 0.0067) and E-Ret (*P < 0.0001)). n = 9 (control) and n = 11 (hM3Dq) mice. f, The effects of CNO on CS-related Ca²⁺ activity during extinction (two-tailed unpaired t-test at minute 35, *P < 0.0001). n = 7 (control) and n = 9 (hM3Dq) mice. g, Combined in vivo Ca²⁺ fibre photometry and astrocyte hM4Di actuation. h, hM4Di-mCherry expression in astrocytes (GFAP) and neurons (NeuN) (two-tailed paired t-test, *P < 0.0001). n = 10 sections, n = 3 mice. Scale bars, 200 μm (left) and 10 μm (right). i, CNO effects on neutral-cage Ca²⁺ activity (two-tailed unpaired t-test at minute 29, *P = 0.0338). n = 8 (control), n = 6 (hM4Di) mice. j, Experimental timeline. k, CNO effects on freezing (two-way repeated-measures ANOVA, with Šídák’s or Fisher’s LSD post hoc tests, comparing control versus hM4Di for Ext block 1 (*P = 0.0048), Ext block 2 (*P = 0.0250) and E-Ret (*P = 0.0005)). n = 9 (control) and n = 12 (hM4Di) mice. l, CNO effects on CS-related Ca²⁺ activity during extinction (two-tailed unpaired t-test at minute 35, *P < 0.0001). n = 8 (control), n = 6 (hM4Di) mice. Controls expressed mCherry (e and k) and mCherry + GfaABC1D GCaMP6f (c, f, i and l). Fluorescence values were z-scored to the 30-min pre-CNO, 3-min pre-extinction or 5-s pre-CS periods. Data are mean ± s.e.m.

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