| Title | Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression |
| Authors | Zhang, Juen Tan, Lubin Ren, Yuqi Liang, Jingwen Lin, Rui Feng, Qiru Zhou, Jingfeng Hu, Fei Ren, Jing Wei, Chao Yu, Tao Zhuang, Yinghua Bettler, Bernhard Wang, Fengchao Luo, Minmin |
| Affiliation | Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. Natl Inst Biol Sci, Beijing 102206, Peoples R China. Peking Univ, PTN Grad Program, Sch Life Sci, Beijing 100081, Peoples R China. Univ Basel, Inst Physiol, Dept Biomed, Pharmazentrum, Klingelbergstr 50-70, CH-4056 Basel, Switzerland. Tsinghua Univ, Sch Life Sci, Beijing 100084, Peoples R China. Luo, MM (reprint author), Natl Inst Biol Sci, Beijing 102206, Peoples R China. |
| Keywords | POSTTRAUMATIC-STRESS-DISORDER CENTRAL-NERVOUS-SYSTEM MEDIAL HABENULA INTERPEDUNCULAR NUCLEUS SYNAPTIC-TRANSMISSION CA2+ CURRENTS EXTINCTION CIRCUITS ANXIETY HIPPOCAMPAL |
| Issue Date | 2016 |
| Publisher | CELL |
| Citation | CELL.2016,166(3),716-728. |
| Abstract | Fear behaviors are regulated by adaptive mechanisms that dampen their expression in the absence of danger. By studying circuits and the molecular mechanisms underlying this adaptive response, we show that cholinergic neurons of the medial habenula reduce fear memory expression through GABA(B) presynaptic excitation. Ablating these neurons or inactivating their GABA(B) receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABA(B) receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABA(B) mediates excitation by amplifying presynaptic Ca2+ entry through Ca-v2.3 channels and potentiating co-release of glutamate, acetylcholine, and neurokinin B to excite interpeduncular neurons. Activating the receptors for these neurotransmitters or enhancing neurotransmission with a phosphodiesterase inhibitor reduces fear responses of both wild-type and GABA(B) mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABA(B) receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders. |
| URI | http://hdl.handle.net/20.500.11897/491827 |
| ISSN | 0092-8674 |
| DOI | 10.1016/j.cell.2016.06.026 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 生命科学学院 |
