TMEM16A expression in cholinergic neurons of the medial habenula mediates anxietyrelated behaviors
- TMEM16A expression in cholinergic neurons of the medial habenula mediates anxietyrelated behaviors
- 이상준; 임혜인; 황은미; 오우택; 정현국; 김아정; ChangHoon Cho; Oleg Yarishkin; Kanghyun Ryoo; YoungSun Lee; Esther Yang; Da Yong Lee; Byeongjun Lee; Hyun Kim; Jae-Yong Park
- Issue Date
- EMBO reports
- VOL 21, e48097
- 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.
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