Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior

Cell Reports

Chun-Chung Chen¹  Jen-Kun Cheng²  Cheng-Chang Lien³  Gábor Tamás⁴  Kazu Nakazawa⁴  Jei-Wei Wu⁵  Kai-Yi Wang⁵  Robert G. Averkin⁵  Wai-Yi Wong⁶ 

[1] Department of Anesthesiology, Mackay Memorial Hospital, Taipei 104, Taiwan;Department of Medicine, Mackay Medical College, New Taipei 252, Taiwan;Department of Neuroscience, Southern Research, Birmingham, AL 35205, USA;ELKH-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged 6726, Hungary;Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;Institute of Physics, Academia Sinica, Taipei 115, Taiwan;

关键词: avoidance behavior;    chemogenetics;    dentate gyrus;    GABA;    mossy cell;    interneuron;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: 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.

【 授权许可】

Unknown