TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety­related behaviors

Title
TMEM16A expression in cholinergic neurons of the medial habenula mediates anxiety­related behaviors
Authors
이상준임혜인황은미오우택정현국김아정Chang­Hoon ChoOleg YarishkinKanghyun RyooYoung­Sun LeeEsther YangDa Yong LeeByeongjun LeeHyun KimJae-Yong Park
Issue Date
2020-02
Publisher
EMBO reports
Citation
VOL 21, e48097
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.
URI
http://pubs.kist.re.kr/handle/201004/70997
ISSN
1469-221X
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KIST Publication > Article
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