title: Dopamine Regulation of Amygdala Inhibitory Circuits for Expression of Learned Fear.
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.
authors.affiliation: 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.
authors.forename: Oh-Bin
authors.initials: OB
authors.lastname: Kwon
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Seungho
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Sanghyeon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Min-Jae
authors.initials: MJ
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Su-Jeong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Bumjin
authors.initials: B
authors.lastname: Ko
authors.affiliation: Department of Physiology, College of Medicine, Seoul National University, Seoul 03080, Korea.
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea.
authors.forename: Sang Ki
authors.initials: SK
authors.lastname: Park
authors.affiliation: 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.
authors.forename: Yun-Beom
authors.initials: YB
authors.lastname: Choi
authors.affiliation: 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.
authors.forename: Craig H
authors.initials: CH
authors.lastname: Bailey
authors.affiliation: 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.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Kandel
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Gyungbuk 37673, Korea. Electronic address: joungkim@postech.ac.kr.
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D005239:Fear / Q000502:physiology* / Q000523:psychology; D057809:HEK293 Cells; D006801:Humans; D007858:Learning / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009924:Organ Culture Techniques; D050638:Receptors, Dopamine D4 / Q000502:physiology*
chemical_list: D050638:Receptors, Dopamine D4; D004298:Dopamine