Cho, Chang-Hoon Lee, Sangjoon Kim, Ajung Yarishkin, Oleg Ryoo, Kanghyun Lee, Young-Sun Jung, Hyun-Gug Yang, Esther Lee, Da Yong Lee, Byeongjun Kim, Hyun Oh, Uhtaek Im, Heh-In Hwang, Eun Mi Park, Jae-Yong 2024-01-19T18:04:54Z 2024-01-19T18:04:54Z 2021-09-04 2020-02 1469-221X https://pubs.kist.re.kr/handle/201004/119039 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. English Nature Publishing Group TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety-related behaviors Article 10.15252/embr.201948097 1 EMBO Reports, v.21, no.2 EMBO Reports 21 2 N scie scopus 000499275500001 2-s2.0-85076169805 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article ACTIVATED CHLORIDE CHANNELS ANOCTAMIN 1 NICOTINE WITHDRAWAL SYNAPTIC RESPONSE RECEPTORS NUCLEUS SEROTONIN PATHWAY MICE TRANSMISSION anxiety cholinergic neurons medial habenula social interaction TMEM16A