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Conditional deletion of TMEM16A in cholinergic neurons of the medial habenula induces anhedonic-like behavior in mice

Authors
Song, Jae GwangKwon, OsungHwang, Eun MiKim, Hyung WookPark, Jae-Yong
Issue Date
24-5월-2022
Publisher
ELSEVIER
Keywords
TMEM16A; Anhedonia; Medial habenula; Cholinergic neuron
Citation
BEHAVIOURAL BRAIN RESEARCH, v.426
Indexed
SCIE
SCOPUS
Journal Title
BEHAVIOURAL BRAIN RESEARCH
Volume
426
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/141724
DOI
10.1016/j.bbr.2022.113841
ISSN
0166-4328
Abstract
The medial habenula (mHb), a subregion of the habenula, is involved in diverse brain functions, such as nicotine addiction, anxiety, and anhedonia. We recently reported that TMEM16A deficiency, a calcium-activated chloride channel, decreased the activity of mHb cholinergic neurons. Since downregulated activity in cholinergic neurons of the mHb is involved in anhedonia-like behavior, we here investigated whether conditional deletion of TMEM16A in mHb cholinergic neurons also displays anhedonia-like behavior. The conditional deletion of TMEM16A in the mHb cholinergic neurons of mice (TMEM16A cKO mice) was generated by crossing ChaT-Cre (+) with floxed TMEM16A f/f mice. TMEM16A cKO mice displayed significantly reduced social interaction, sucrose preference, female urine sniffing, and increased marble burying. These behavioral data suggest the potential role of TMEM16A in anhedonic-like behavior in mice. Taken together, the presented data suggest that TMEM16A-mediated mHb activity might be a therapeutic target for anhedonia-related symptoms.
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