Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan.
Department of Medicine, Mackay Medical College, New Taipei 252, Taiwan; Department of Anesthesiology, Mackay Memorial Hospital, Taipei 104, Taiwan.
Cell Rep. 2021 Sep 14;36(11):109702. doi: 10.1016/j.celrep.2021.109702.
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.
调节海马齿状回（DG）兴奋性可调节焦虑。在 DG 中，谷氨酸能苔藓细胞（MCs）接收来自主颗粒细胞（GCs）的兴奋性驱动，并介导 GCs 的反馈兴奋和抑制。然而，MCs 调节通过海马回路的焦虑相关信息路由的电路机制尚不清楚。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，我们首先通过钙光纤光度法证明，当小鼠探索焦虑环境时，其腹侧海马体（vHPC）中的 MC 活动增加。接下来，细胞外记录显示，MC 的光遗传学激活优先募集 GABA 能神经元，从而抑制 GCs 和腹侧 CA1 神经元。最后，vHPC 中 MC 的化学遗传刺激可减少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。
