Modulation of hippocampal dentate gyrus (DG) excitability regulates anxiety. In the DG, glutamatergic mossy cells (MCs) receive the excitatory drive from principal granule cells (GCs) and mediate the feedback excitation and inhibition of GCs. However, the circuit mechanism by which MCs regulate anxiety-related information routing through hippocampal circuits remains unclear. Moreover, the correlation between MC activity and anxiety states is unclear. In this study, we first demonstrate, by means of calcium fiber photometry, that MC activity in the ventral hippocampus (vHPC) of mice increases while they explore anxiogenic environments. Next, juxtacellular recordings reveal that optogenetic activation of MCs preferentially recruits GABAergic neurons, thereby suppressing GCs and ventral CA1 neurons. Finally, chemogenetic excitation of MCs in the vHPC reduces avoidance behaviors in both healthy and anxious mice. These results not only indicate an anxiolytic role of MCs but also suggest that MCs may be a potential therapeutic target for anxiety disorders.

海马齿状回 (DG) 兴奋性的调节调节焦虑。在 DG 中，谷氨酸能苔藓细胞 (MCs) 接受来自主要颗粒细胞 (GCs) 的兴奋性驱动，并介导 GCs 的反馈兴奋和抑制。然而，MCs 通过海马回路调节焦虑相关信息路由的回路机制仍不清楚。此外，MC 活动与焦虑状态之间的相关性尚不清楚。在这项研究中，我们首先通过钙纤维光度法证明，小鼠在探索焦虑环境时，腹侧海马 (vHPC) 中的 MC 活性会增加。接下来，近细胞记录显示 MCs 的光遗传学激活优先招募 GABAergic 神经元，从而抑制 GCs 和腹侧 CA1 神经元。最后，vHPC 中 MC 的化学遗传学激发减少了健康和焦虑小鼠的回避行为。这些结果不仅表明 MCs 具有抗焦虑作用，而且表明 MCs 可能是焦虑症的潜在治疗靶点。