title: Region-specific roles of the prelimbic cortex, the dorsal CA1, the ventral DG and ventral CA1 of the hippocampus in the fear return evoked by a sub-conditioning procedure in rats.
abstract: The return of learned fear is an important issue in anxiety disorder research since an analogous process may contribute to long-term fear maintenance or clinical relapse. A number of studies demonstrate that mPFC and hippocampus are important in the modulation of post-extinction re-expression of fear memory. However, the region-specific role of these structures in the fear return evoked by a sub-threshold conditioning (SC) is not known. In the present experiments, we first examined specific roles of the prelimbic cortex (PL), the dorsal hippocampus (DH, the dorsal CA1 area in particular), the ventral hippocampus (the ventral dentate gyrus (vDG) and the ventral CA1 area in particular) in this fear return process. Then we examined the role of connections between PL and vCA1 with this behavioral approach. Rats were subjected to five tone-shock pairings (1.0-mA shock) to induce conditioned fear (freezing), followed by three fear extinction sessions (25 tone-alone trials each session). After a post-test for extinction memory, some rats were retrained with the SC procedure to reinstate tone-evoked freezing. Rat groups were injected with low doses of the GABAA agonist muscimol to selectively inactivate PL, DH, vDG, or vCA1 120 min before the fear return test. A disconnection paradigm with ipsilateral or contralateral muscimol injection of the PL and the vCA1 was used to examine the role of this pathway in the fear return. We found that transient inactivation of these areas significantly impaired fear return (freezing): inactivation of the prelimbic cortex blocked SC-evoked fear return in particular but did not influence fear expression in general; inactivation of the DH area impaired fear return, but had no effect on the extinction retrieval process; both ventral DG and ventral CA1 are required for the return of extinguished fear whereas only ventral DG is required for the extinction retrieval. These findings suggest that PL, DH, vDG, and vCA1 all contribute to the fear return and connections between PL and vCA1 may be involved in the modulation of this process.
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China; University of Chinese Academy of Sciences, Beijing, PR China; Department of Life Sciences, Binzhou University, Binzhou, Shandong Province, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Fu
authors.affiliation: School of Education Science, Henan University, Kaifeng, Henan Province, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xing
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China; University of Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Mengfi
authors.initials: M
authors.lastname: Han
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China; University of Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Xu
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Chengji
authors.initials: C
authors.lastname: Piao
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China; University of Chinese Academy of Sciences, Beijing, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China. Electronic address: Zhengxg@psych.ac.cn.
authors.forename: Xigeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004597:Electroshock; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D009118:Muscimol / Q000008:administration & dosage; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D009118:Muscimol
keywords: Fear return; Hippocampus; Prelimbic cortex; Sub-conditioning procedure