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Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice.
Neuroscience 2018; 388:448-459N

Abstract

Anxiety disorder is a major psychiatric disorder characterized by fear, worry, and excessive rumination. However, the molecular mechanisms underlying neural plasticity and anxiety remain unclear. Here, we utilized a mouse model of anxiety-like behaviors induced by the chronic administration of corticosterone (CORT) to determine the exact mechanism of each region of the fear circuits in the anxiety disorders. Chronic CORT-treated mice showed a significant increase in anxiety-related behaviors as assessed by the elevated plus maze, light-dark, open-field, and marble-burying tasks. In addition, chronic CORT-treated mice exhibited abnormal amygdala-dependent tone-induced fear memory but normal hippocampus-dependent contextual memory. Consistent with amygdala hyperactivation, chronic CORT-treated mice showed significantly increased numbers of c-Fos-positive cells in the basolateral amygdala (BLA) after tone stimulation. Long-term potentiation (LTP) was markedly enhanced in the BLA of chronic CORT-treated mice compared to that of vehicle-treated mice. Immunoblot analyses revealed that autophosphorylation of Ca2+/calmodulin-dependent protein kinase (CaMK) IIα at threonine 286 and phosphorylation of cyclic-adenosine-monophosphate response-element-binding protein (CREB) at serine 133 were markedly increased in the BLA of chronic CORT-treated mice after tone stimulation. The protein and mRNA levels of brain-derived neurotrophic factor (BDNF) also significantly increased. Our findings suggest that increased CaMKII activity and synaptic plasticity in the BLA likely account for the aberrant amygdala-dependent fear memory in chronic CORT-treated mice.

Authors+Show Affiliations

Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. Electronic address: ryo.inagaki.r5@dc.tohoku.ac.jp.Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. Electronic address: shigeki@m.tohoku.ac.jp.Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan. Electronic address: kfukunaga@m.tohoku.ac.jp.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30118751

Citation

Inagaki, Ryo, et al. "Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice." Neuroscience, vol. 388, 2018, pp. 448-459.
Inagaki R, Moriguchi S, Fukunaga K. Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice. Neuroscience. 2018;388:448-459.
Inagaki, R., Moriguchi, S., & Fukunaga, K. (2018). Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice. Neuroscience, 388, pp. 448-459. doi:10.1016/j.neuroscience.2018.08.004.
Inagaki R, Moriguchi S, Fukunaga K. Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice. Neuroscience. 2018 09 15;388:448-459. PubMed PMID: 30118751.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice. AU - Inagaki,Ryo, AU - Moriguchi,Shigeki, AU - Fukunaga,Kohji, Y1 - 2018/08/16/ PY - 2017/12/07/received PY - 2018/08/02/revised PY - 2018/08/06/accepted PY - 2018/8/18/pubmed PY - 2019/3/30/medline PY - 2018/8/18/entrez KW - CaMKII KW - amygdala KW - corticosterone KW - fear memory KW - long-term potentiation SP - 448 EP - 459 JF - Neuroscience JO - Neuroscience VL - 388 N2 - Anxiety disorder is a major psychiatric disorder characterized by fear, worry, and excessive rumination. However, the molecular mechanisms underlying neural plasticity and anxiety remain unclear. Here, we utilized a mouse model of anxiety-like behaviors induced by the chronic administration of corticosterone (CORT) to determine the exact mechanism of each region of the fear circuits in the anxiety disorders. Chronic CORT-treated mice showed a significant increase in anxiety-related behaviors as assessed by the elevated plus maze, light-dark, open-field, and marble-burying tasks. In addition, chronic CORT-treated mice exhibited abnormal amygdala-dependent tone-induced fear memory but normal hippocampus-dependent contextual memory. Consistent with amygdala hyperactivation, chronic CORT-treated mice showed significantly increased numbers of c-Fos-positive cells in the basolateral amygdala (BLA) after tone stimulation. Long-term potentiation (LTP) was markedly enhanced in the BLA of chronic CORT-treated mice compared to that of vehicle-treated mice. Immunoblot analyses revealed that autophosphorylation of Ca2+/calmodulin-dependent protein kinase (CaMK) IIα at threonine 286 and phosphorylation of cyclic-adenosine-monophosphate response-element-binding protein (CREB) at serine 133 were markedly increased in the BLA of chronic CORT-treated mice after tone stimulation. The protein and mRNA levels of brain-derived neurotrophic factor (BDNF) also significantly increased. Our findings suggest that increased CaMKII activity and synaptic plasticity in the BLA likely account for the aberrant amygdala-dependent fear memory in chronic CORT-treated mice. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/30118751/Aberrant_Amygdala_dependent_Fear_Memory_in_Corticosterone_treated_Mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(18)30542-6 DB - PRIME DP - Unbound Medicine ER -