Department of Physiology, University of California, San Francisco, San Francisco, United States.
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States.
Elife. 2019 Sep 4;8:e47106. doi: 10.7554/eLife.47106.
TMEM16B (ANO2) is the Ca-activated chloride channel expressed in multiple brain regions, including the amygdala. Here we report that knockout mice exhibit impaired anxiety-related behaviors and context-independent fear memory, thus implicating TMEM16B in anxiety modulation. We found that TMEM16B is expressed in somatostatin-positive (SOM) GABAergic neurons of the central lateral amygdala (CeL), and its activity modulates action potential duration and inhibitory postsynaptic current (IPSC). We further provide evidence for TMEM16B actions not only in the soma but also in the presynaptic nerve terminals of GABAergic neurons. Our study reveals an intriguing role for TMEM16B in context-independent but not context-dependent fear memory, and supports the notion that dysfunction of the amygdala contributes to anxiety-related behaviors.
TMEM16B（ANO2）是一种在多个脑区表达的 Ca2+激活氯离子通道，包括杏仁核。在这里，我们报告说 knockout 小鼠表现出焦虑相关行为受损和情境独立性恐惧记忆缺失，这表明 TMEM16B 参与了焦虑的调节。我们发现 TMEM16B 表达在中央外侧杏仁核（CeL）的生长抑素阳性（SOM）GABA 能神经元中，其活性调节动作电位持续时间和抑制性突触后电流（IPSC）。我们进一步提供证据表明 TMEM16B 的作用不仅在神经元体中，而且在 GABA 能神经元的突触前神经末梢中。我们的研究揭示了 TMEM16B 在情境独立性而非情境依赖性恐惧记忆中的作用，支持了杏仁核功能障碍导致焦虑相关行为的观点。
