Long-Lasting Increase of Corticosterone After Fear Memory Reactivation: Anxiolytic Effects and Network Activity Modulation in the Ventral Hippocampus

Publication Type:

Journal Article

Source:

Neuropsychopharmacology, Volume 38, p.386–394 (2013)

ISBN:

1740-634X (Electronic)00

DOI Name (links to online publication)

10.1038/npp.2012.192

Keywords:

corticosterone; anxiety; fear memory; gamma oscillations; ventral hippocampus

Abstract:

Pathological fear and anxiety can be studied, in rodents, with fear conditioning and exposure to reminder cues. These paradigms are thought to critically involve the ventral hippocampus, which also serves as key site of glucocorticoid action in the brain. Here, we demonstrate a long-lasting reduction of kainate-induced gamma oscillations in slice preparations of the ventral hippocampal area CA3, 30 days after a single fear conditioning training. Reduction of gamma power was sensitive to corticosterone application and associated with a decrease in glucocorticoid and mineralocorticoid receptor mRNA expression across strata of the ventral hippocampal CA3. A fear reactivation session 24 h after the initial conditioning normalized receptor expression levels and attenuated the corticosterone-mediated recovery of gamma oscillations. It moreover increased both baseline and stimulus-induced corticosterone plasma levels and evoked a generalization of fear memory to the background context. Reduced ventral hippocampal gamma oscillation in both fear reactivated and non-reactivated mice were associated with a decrease of anxiety-like behavior in an elevated plus maze. Taking advantage of the circadian fluctuation in corticosterone, we demonstrated the association of high endogenous basal corticosterone plasma concentrations during morning hours with reduced anxiety-like behavior in fear reactivated mice. The anxiolytic effect of the hormone was verified with local applications to the ventral hippocampus. Our data suggest that corticosterone acting on ventral hippocampal network activity has anxiolytic-like effects following fear exposure, highlighting its potential therapeutic value for anxiety disorders.Neuropsychopharmacology advance online publication, 12 September 2012; doi:10.1038/npp.2012.192.

18/01/2013