title: Fear Erasure Facilitated by Immature Inhibitory Neuron Transplantation.
abstract: Transplantation of embryonic γ-aminobutyric acid (GABA)ergic neurons has been shown to modify disease phenotypes in rodent models of neurologic and psychiatric disorders. However, whether transplanted interneurons modulate fear memory remains largely unclear. Here, we report that transplantation of embryonic interneurons into the amygdala does not alter host fear memory formation. Yet approximately 2 weeks after transplantation, but not earlier or later, extinction training produces a marked reduction in spontaneous recovery and renewal of fear response. Further analyses reveal that transplanted interneurons robustly form functional synapses with neurons of the host amygdala and exhibit similar developmental maturation in electrophysiological properties as native amygdala interneurons. Importantly, transplanted immature interneurons reduce the expression of perineuronal nets, promote long-term synaptic plasticity, and modulate both excitatory and inhibitory synaptic transmissions of the host circuits. Our findings demonstrate that transplanted immature interneurons modify amygdala circuitry and suggest a previously unknown strategy for the prevention of extinction-resistant pathological fear.
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Wu-Zhou
authors.initials: WZ
authors.lastname: Yang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Cao
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xuan-Fu
authors.initials: XF
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 200433, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Su
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin-Long
authors.initials: BL
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Hu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Lin-Yun
authors.initials: LY
authors.lastname: Liu
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Ma
authors.affiliation: Institutes of Brain Science, State Key Laboratory of Medical Neurobiology and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; School of Life Sciences, Fudan University, Shanghai 200433, China; School of Basic Medical Sciences, Fudan University, Shanghai 200433, China. Electronic address: ycyu@fudan.edu.cn.
authors.forename: Yong-Chun
authors.initials: YC
authors.lastname: Yu
mesh_terms: D000679:Amygdala / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001522:Behavior, Animal; D003214:Conditioning, Classical / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism / Q000637:transplantation*; D008568:Memory / Q000502:physiology*; D051379:Mice; D009433:Neural Inhibition / Q000502:physiology; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques
keywords: amygdala; embryonic interneuron; fear extinction; fear recovery; immature neuron; synaptic plasticity; transplantation