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Neuron. 2015 Oct 21;88(2):378-89. doi: 10.1016/j.neuron.2015.09.001. Epub 2015 Sep 24.

Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear.

Author information

1
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea; Daegu-Gyeongbuk Medical Innovation Foundation, New Drug Development Center, Daegu 41061, Korea.
2
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
3
Department of Physiology, College of Medicine, Seoul National University, Seoul 03080, Korea.
4
Department of Neuroscience, Kavli Institute of Brain Science, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA.
5
Department of Neuroscience, Kavli Institute of Brain Science, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA; Howard Hughes Medical Institute, New York, NY 10032, USA.
6
Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea. Electronic address: joungkim@postech.ac.kr.

Abstract

GABAergic signaling in the amygdala controls learned fear, and its dysfunction potentially contributes to posttraumatic stress disorder (PTSD). We find that sub-threshold fear conditioning leads to dopamine receptor D4-dependent long-term depression (LTD) of glutamatergic excitatory synapses by increasing inhibitory inputs onto neurons of the dorsal intercalated cell mass (ITC) in the amygdala. Pharmacological, genetic, and optogenetic manipulations of the amygdala regions centered on the dorsal ITC reveal that this LTD limits less salient experiences from forming persistent memories. In further support of the idea that LTD has preventive and discriminative roles, we find that LTD at the dorsal ITC is impaired in mice exhibiting PTSD-like behaviors. These findings reveal a novel role of inhibitory circuits in the amygdala, which serves to dampen and restrict the level of fear expression. This mechanism is interfered with by stimuli that give rise to PTSD and may also be recruited for fear-related psychiatric diseases.

PMID:
26412489
DOI:
10.1016/j.neuron.2015.09.001
[Indexed for MEDLINE]
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