title: Maternal separation exaggerates spontaneous recovery of extinguished contextual fear in adult female rats.
abstract: Early life stress increases the risk of posttraumatic stress disorders (PTSD). Patients with PTSD show impaired extinction of traumatic memory, and in women, this occurs more often when PTSD is preceded by child trauma. However, it is still unclear how early life stress accounts for extinction impairment. Here, we studied the effects of maternal separation (MS, postnatal day 2 to 14) on contextual fear extinction in adult female rats. Additionally, to examine changes in synaptic function affected by MS, we measured long-term potentiation (LTP) in prefrontal cortex and hippocampus in vitro, both of which have been implicated in fear extinction. We found that adult female rats had been subjected to MS exhibited significant spontaneous recovery of fear to the extinguished context. Furthermore, MS exposure resulted in LTP impairment in both infralimbic prefrontal cortex layer 2/3-layer 5 and hippocampal SC-CA1 pathways. Interestingly, no obvious effects of MS on contextual fear conditioning, fear recall as well as extinction training and recall were observed. Innate fear in the elevated plus maze or open field test remained nearly unaffected. These findings provided the first evidence that MS may exaggerate spontaneous recovery after contextual fear extinction, for which LTP impairment in the medial prefrontal cortex and hippocampus may be responsible, thereby possibly leading to impaired extinction associated with PTSD.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan 650223, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Gui-Jing
authors.initials: GJ
authors.lastname: Xiong
authors.affiliation: Department of Physiology, Kunming Medical University, Kunming, Yunnan 650500, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan 650223, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan 650223, China. Electronic address: lxu@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms, and KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Disease, and Laboratory of Learning and Memory, Kunming Institute of Zoology, Chinese Academy of Science, Kunming, Yunnan 650223, China. Electronic address: talktomaomao@163.com.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Mao
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology*; D005106:Exploratory Behavior / Q000502:physiology; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology; D008426:Maternal Deprivation; D018782:Maze Learning / Q000502:physiology; D011939:Mental Recall / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000503:physiopathology; D046509:Tissue Culture Techniques
keywords: Contextual fear extinction; Female; Long-term potentiation; Maternal separation; Spontaneous recovery