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. 2021 Dec 17;145(8):2806–2822. doi: 10.1093/brain/awab460

Figure 4.

Figure 4

MRIgFUS-mediated delivery of D3 enhances cholinergic function in hippocampal and cortical areas. (A) Representative confocal images from non-Tg PBS, TgCRND8 PBS, PBS/FUS, D3 or D3/FUS-treated mice at 6.5 months of age show ChAT+ fibres in the hippocampus and prefrontal cortex. A decrease in ChAT+ fibre density in CA1 subfield of the hippocampus was apparent in PBS-treated TgCRND8 mice relative to non-Tg mice. A decrease in cholinergic innervation was also found across cortical layers in PBS-treated TgCRND8 mice compared to non-Tg controls. D3/FUS treatment increased cholinergic innervation throughout the prefrontal cortex and CA1. (B–D) D3/FUS promoted (B) basal and depolarization–induced ACh release from hippocampal and cortical slices, (C) tissue ACh content in the hippocampus and cortex and (D) AChE activity in these regions. Scale bar in A = 50 μm. Statistics: (B) two-way or (C and D) one-way ANOVA with Holm-Sidak post hoc test. Significance: *,+,†,#P < 0.05; **,++,††,##P < 0.01, ***,+++,†††,###P < 0.001; #Comparison with basal ACh release of the same treatment group (depolarization effect). †Comparison of D3-treated TgCRND8 mice with PBS-treated non-Tg mice (genotype effect). +Comparison of PBS/FUS-treated with D3/FUS-treated TgCRND8 mice (D3 effect). *Comparison of D3-treated TgCRND8 mice with D3/FUS-treated TgCRND8 mice (D3/FUS effect). Data represent means ± SEM; n = 6 per group. or = stratum oriens; pyr = stratum pyrimidale; rad = stratum radiatum; lm = stratum lacunosum moleculare.