@article{b086949a2395481da5a9727df35fb149,
title = "TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety-related behaviors",
abstract = "TMEM16A, a Ca2+-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.",
keywords = "TMEM16A, anxiety, cholinergic neurons, medial habenula, social interaction",
author = "Cho, {Chang Hoon} and Sangjoon Lee and Ajung Kim and Oleg Yarishkin and Kanghyun Ryoo and Lee, {Young Sun} and Jung, {Hyun Gug} and Esther Yang and Lee, {Da Yong} and Byeongjun Lee and Hyun Kim and Uhtaek Oh and Im, {Heh In} and Hwang, {Eun Mi} and Park, {Jae Yong}",
note = "Funding Information: This work was supported by the Bio-Synergy Research Project (NRF-2017M3A9C4092979 to J-YP) and the Basic Science Research Program (NRF-2016M3C7A1904149 and NRF-2017M3C7A1079694 to J-YP) from the National Research Foundation in Korea. This work was also supported by the National Research Council of Science & Technology of the Korean government (No.CRC-15-04-KIST to H-II) and KBRI basic research program through Korea Brain Research Institute funded by Ministry of Science and ICT(19-BR-03-02 to EMH). Funding Information: This work was supported by the Bio‐Synergy Research Project (NRF‐2017M3A9C4092979 to J‐YP) and the Basic Science Research Program (NRF‐2016M3C7A1904149 and NRF‐2017M3C7A1079694 to J‐YP) from the National Research Foundation in Korea. This work was also supported by the National Research Council of Science & Technology of the Korean government (No.CRC‐15‐04‐KIST to H‐II) and KBRI basic research program through Korea Brain Research Institute funded by Ministry of Science and ICT(19‐BR‐03‐02 to EMH). Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2020",
month = feb,
day = "5",
doi = "10.15252/embr.201948097",
language = "English",
volume = "21",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "2",
}