Fig. 9: Adenosine/A2a activation improves social memory.

a, b Microdialysis measurement of ventral hippocampal adenosine. c Increased extracellular adenosine in GFAP-NLG3 WT (n = 5 mice, p = 0.0144), not in GFAP-NLG3 KO (n = 5 mice), after social stimulation. RFU: Relative Fluorescence Units. ΔRFU: Post-social RFU minus Pre-social RFU. d AAV virus construct and expression of GRABado. e Increased adenosine signals after sniffings in WT (n = 8 recordings, 4 mice), not in GFAP-NLG3 KO mice (n = 8 recordings, 4 mice). f Reduced GRABado signals after sniffings in GFAP-NLG3 KO mice (n = 8 recordings, 4 mice, p = 0.0325). g Systemic CGS 21680 injections. h GFAP-NLG3 KO mice treated with saline (n = 6 mice, p < 0.001) or CGS 21680 (n = 10 mice, p < 0.001) preferred S1 over E. i GFAP-NLG3 KO mice treated with CGS 21680 (n = 10 mice, p < 0.001), not with saline (n = 6 mice), preferred S2 over S1 (memory index p = 0.0111). j, k AAV virus construct and injection for ventral hippocampal neuronal A2a deletion. l CaMKIIα-EGFP-2A-Cre expression in ventral hippocampus and CA1 neurons (repeated 5 times). m WT and A2a f/f mice injected with CaMKIIα-EGFP-Cre virus preferred S1 over E (n = 7 mice, p < 0.001). n CaMKIIα-EGFP-Cre virus injected WT (p < 0.001), not A2a f/f mice, preferred S2 over S1 (n = 7 mice, memory index p = 0.000161). o Reduced A2a receptor protein in A2a f/f mice injected with CaMKIIα-EGFP-Cre virus (n = 5 mice, p = 0.00174). p Impaired LTP in A2a f/f mice injected with CaMKIIα-EGFP-Cre virus (n = 5 slices, 3 mice, p = 0.00117). Data represent mean ± SEM; two-tailed t test for (c, f, o), and right panels of (i, n, and p); two-way ANOVA with Tukey post hoc multiple comparisons for (h, m), and left panels of (i and n); *p < 0.05, **p < 0.01, ***p < 0.001. Scale bars: 200 μm in left panel of (l), 50 μm in right panel of (l), 0.25 mV/50 ms in (p). Source data are provided as a Source Data file.