TY - JOUR N1 - Funding Agency and Grant Number: Brain Research Center, National Yang Ming Chiao Tung University from the Featured Areas Research Center Program; Ministry of Science and Technology (MOST) in TaiwanMinistry of Science and Technology, Taiwan [106-2320-B-010-011-MY3, 106-2923-B-010-001-MY3, 108-2923-B-010001-MY2, 108-2911-I-010-504, 108-2321-B-010-009-MY2, 108-2320-B010-026-MY3, 108-2638-B-010-002-MY2, 110-2321-B-010-006, 105-2911-I-010-508]; National Health Research InstitutesNational Health Research Institutes, Japan [NHRI-EX110-10814NI] Funding text: We thank F. Ferraguti (University of Innsbruck, Austria), A. Dominique (University of Liege, Belgium), H.J. Cheng (Academia Sinica, Taiwan), H. Lu (George Washington University, USA), C.H. Wang (RIKEN, Japan), and J. Song (University of North Carolina, USA) for commenting on an earlier version of the manuscript, and all of the members of the Lien lab for insightful discussions. This work was financially supported by the Brain Research Center, National Yang Ming Chiao Tung University from the Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education in Taiwan, National Health Research Institutes (NHRI-EX110-10814NI), and the Ministry of Science and Technology (MOST; 106-2320-B-010-011-MY3, 106-2923-B-010-001-MY3, 108-2923-B-010001-MY2, 108-2911-I-010-504, 108-2321-B-010-009-MY2, 108-2320-B010-026-MY3, 108-2638-B-010-002-MY2, 110-2321-B-010-006, MOSTHAS Project-based Personnel Exchange Program 105-2911-I-010-508) in Taiwan. A1 - Wang Kai-Yi A1 - Wu Jei-Wei A1 - Cheng Jen-Kun A1 - Chen Chun-Chung A1 - Wong Wai-Yi A1 - Averkin Róbert A1 - Tamás Gábor A1 - Nakazawa Kazu A1 - Lien Cheng-Chang ID - publicatio29407 TI - Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior Y1 - 2021/// IS - 11 VL - 36 AV - public JF - CELL REPORTS N2 - 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. SN - 2211-1247 UR - https://doi.org/10.1016/j.celrep.2021.109702 EP - 19 ER -