Presynaptic Excitation via GABAB Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression.
- Zhang J School of Life Sciences, Tsinghua University, Beijing 100084, China; National Institute of Biological Sciences, Beijing 102206, China.
- Tan L School of Life Sciences, Tsinghua University, Beijing 100084, China; National Institute of Biological Sciences, Beijing 102206, China.
- Ren Y National Institute of Biological Sciences, Beijing 102206, China; PTN Graduate Program, Peking University School of Life Sciences, Beijing 100081, China.
- Liang J National Institute of Biological Sciences, Beijing 102206, China.
- Lin R National Institute of Biological Sciences, Beijing 102206, China; PTN Graduate Program, Peking University School of Life Sciences, Beijing 100081, China.
- Feng Q National Institute of Biological Sciences, Beijing 102206, China.
- Zhou J National Institute of Biological Sciences, Beijing 102206, China; PTN Graduate Program, Peking University School of Life Sciences, Beijing 100081, China.
- Hu F National Institute of Biological Sciences, Beijing 102206, China.
- Ren J National Institute of Biological Sciences, Beijing 102206, China.
- Wei C National Institute of Biological Sciences, Beijing 102206, China.
- Yu T National Institute of Biological Sciences, Beijing 102206, China.
- Zhuang Y National Institute of Biological Sciences, Beijing 102206, China.
- Bettler B Department of Biomedicine, Institute of Physiology, Pharmazentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
- Wang F National Institute of Biological Sciences, Beijing 102206, China.
- Luo M School of Life Sciences, Tsinghua University, Beijing 100084, China; National Institute of Biological Sciences, Beijing 102206, China. Electronic address: luominmin@nibs.ac.cn.
- 2016-07-19
Published in:
- Cell. - 2016
Animals
Calcium
Calcium Channels
Cholinergic Neurons
Fear
Female
Habenula
Male
Memory
Mice
Mice, Inbred C57BL
Neural Pathways
Neurotransmitter Agents
Receptors, GABA-B
Synaptic Transmission
English
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 GABAB presynaptic excitation. Ablating these neurons or inactivating their GABAB receptors impairs fear extinction in mice, whereas activating the neurons or their axonal GABAB receptors reduces conditioned fear. Although considered exclusively inhibitory, here, GABAB mediates excitation by amplifying presynaptic Ca(2+) entry through Cav2.3 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 GABAB mutant mice. We identify the role of an extra-amygdalar circuit and presynaptic GABAB receptors in fear control, suggesting that boosting neurotransmission in this pathway might ameliorate some fear disorders.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1016/j.cell.2016.06.026
- PMID 27426949
- Persistent URL
- https://sonar.ch/global/documents/232198
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