Elevation of hilar mossy cell activity suppresses hippocampal excitability and avoidance behavior
Kai-Yi Wang,
Jei-Wei Wu,
Jen-Kun Cheng,
Chun-Chung Chen,
Wai-Yi Wong,
Robert G. Averkin,
Gábor Tamás,
Kazu Nakazawa,
Cheng-Chang Lien
Affiliations
Kai-Yi Wang
Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
Jei-Wei Wu
Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
Jen-Kun Cheng
Department of Medicine, Mackay Medical College, New Taipei 252, Taiwan; Department of Anesthesiology, Mackay Memorial Hospital, Taipei 104, Taiwan
Chun-Chung Chen
Institute of Physics, Academia Sinica, Taipei 115, Taiwan
Wai-Yi Wong
Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
Robert G. Averkin
ELKH-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged 6726, Hungary
Gábor Tamás
ELKH-SZTE Research Group for Cortical Microcircuits, Department of Physiology, Anatomy and Neuroscience, University of Szeged, Közép fasor 52, Szeged 6726, Hungary
Kazu Nakazawa
Department of Neuroscience, Southern Research, Birmingham, AL 35205, USA; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA
Cheng-Chang Lien
Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Brain Research Center, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan; Corresponding author
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.
