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 in

SUBMITTER: Cho CH 

PROVIDER: S-EPMC7001509 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature