Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice. (15th September 2018)

• Record Type: Journal Article
• Authors: Inagaki, Ryo; Moriguchi, Shigeki; Fukunaga, Kohji
• Is Part Of: Neuroscience. Volume 388(2018)
• Page Start: 448
• Page End: 459
• Publication Date: 2018-09-15
• Subjects: corticosterone -- fear memory -- CaMKII -- amygdala -- long-term potentiation; AC auditory cortex -- AMPAR α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor -- BDNF brain-derived neurotrophic factor -- BLA basolateral amygdala -- CaMK Ca2+/calmodulin-dependent protein kinase -- CeA central amygdala -- CORT corticosterone -- CREB cyclic-adenosine-monophosphate response-element-binding protein -- CS conditioned stimulus -- EDTA ethylenediaminetetraacetic acid -- EGTA ethylene glycol-bis(β-aminoethyl ether)-N, N, N′, N′-tetraacetic acid -- ERK extracellular-signal-regulated kinase -- fEPSP field excitatory post-synaptic potential -- GR glucocorticoid receptor -- HFS high-frequency stimulation -- HPA hypothalamic−pituitaryadrenal -- LA lateral amygdala -- LTP long-term potentiation -- MAP mitogen-activated protein -- NA noradrenaline -- NMDAR N-methyl-d-aspartate receptor -- single-CORT single-corticosterone-treated -- US unconditioned stimulus; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.08.004
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Chronic corticosterone-treated mice exhibit impaired amygdala-dependent fear memory. Corticosterone treatment increased Ca 2+ /calmodulin-dependent kinase autophosphorylation in the basolateral amygdala. Long-term potentiation was markedly enhanced in the basolateral amygdala of chronic-corticosterone-treated mice. Increased synaptic plasticity in the basolateral amygdala may underlie abnormal fear memory in corticosterone-treated mice. 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 Ca 2+ /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.