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TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety‐related behaviors
Author(s) -
Cho ChangHoon,
Lee Sangjoon,
Kim Ajung,
Yarishkin Oleg,
Ryoo Kanghyun,
Lee YoungSun,
Jung HyunGug,
Yang Esther,
Lee Da Yong,
Lee Byeongjun,
Kim Hyun,
Oh Uhtaek,
Im HehIn,
Hwang Eun Mi,
Park JaeYong
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201948097
Subject(s) - habenula , neuroscience , cholinergic , anxiety , cholinergic neuron , biology , psychology , microbiology and biotechnology , forebrain , central nervous system , psychiatry
TMEM16A, a Ca 2+ ‐activated Cl − channel, is known to modulate the excitability of various types of cells; however, its function in central neurons is largely unknown. Here, we show the specific expression of TMEM16A in the medial habenula (mHb) via RNAscope in situ hybridization, immunohistochemistry, and electrophysiology. When TMEM16A is ablated in the mHb cholinergic neurons (TMEM16A cKO mice), the slope of after‐hyperpolarization of spontaneous action potentials decreases and the firing frequency is reduced. Reduced mHb activity also decreases the activity of the interpeduncular nucleus (IPN). Moreover, TMEM16A cKO mice display anxiogenic behaviors and deficits in social interaction without despair‐like phenotypes or cognitive dysfunctions. Finally, chemogenetic inhibition of mHb cholinergic neurons using the DREADD (Designer Receptors Exclusively Activated by Designer Drugs) approach reveals similar behavioral phenotypes to those of TMEM16A cKO mice. We conclude that TMEM16A plays a key role in anxiety‐related behaviors regulated by mHb cholinergic neurons and could be a potential therapeutic target against anxiety‐related disorders.