title: Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.
abstract: Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Ji-Hong
authors: JH
authors: Liu
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Qiang-Long
authors: QL
authors: You
authors: Department of Pharmacy, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510630, China.
authors: Mei-Dan
authors: MD
authors: Wei
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Qian
authors: Q
authors: Wang
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Zheng-Yi
authors: ZY
authors: Luo
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Song
authors: S
authors: Lin
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Lang
authors: L
authors: Huang
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Shu-Ji
authors: SJ
authors: Li
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China.
authors: Xiao-Wen
authors: XW
authors: Li
authors: State Key Laboratory of Organ Failure Research, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. tgao@smu.edu.cn.|Key Laboratory of Psychiatric Disorders of Guangdong Province, Southern Medical University, Guangzhou, 510515, China. tgao@smu.edu.cn.
authors: Tian-Ming
authors: TM
authors: Gao
mesh_terms: D000293:Adolescent; D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000503:physiopathology*; D003214:Conditioning, Classical; D004558:Electric Stimulation; D004640:Emetine / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005106:Exploratory Behavior; D005239:Fear / Q000187:drug effects / Q000502:physiology / Q000523:psychology*; D006801:Humans; D007398:Interpersonal Relations; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D023421:Models, Animal; D009419:Nerve Tissue Proteins / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D000297:Psychology, Adolescent; D020813:Receptor, trkB / Q000037:antagonists & inhibitors / Q000502:physiology; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology; D012934:Social Isolation / Q000523:psychology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; D020813:Receptor, trkB; D004640:Emetine
keywords: BDNF; Fear memory; Long-term potentiation; Social isolation; TrkB receptor