Hippocampal corticosterone impairs memory consolidation during sleep but improves consolidation in the wake state

Abstract

We studied the interaction between glucocorticoid (GC) level and sleep/wake state during memory consolidation. Recent research has accumulated evidence that sleep supports memory consolidation in a unique physiological process, qualitatively distinct from consolidation occurring during wakefulness. This appears particularly true for memories that rely on the hippocampus, a region with abundant expression of GC receptors. Against this backdrop we hypothesized that GC effects on consolidation depend on the brain state, i.e., sleep and wakefulness. Following exploration of two objects in an open field, during 80 min retention periods rats received an intrahippocampal infusion of corticosterone (10 ng) or vehicle while asleep or awake. Then the memory was tested in the hippocampus-dependent object-place recognition paradigm. GCs impaired memory consolidation when administered during sleep but improved consolidation during the wake retention interval. Intrahippocampal infusion of GC or sleep/wake manipulations did not alter novel-object recognition performance that does not require the hippocampus. This work corroborates the notion of distinct consolidation processes occurring in sleep and wakefulnesss, and identifies GCs as a key player controlling distinct hippocampal memory consolidation processes in sleep and wake conditions.

Keywords: glucocorticoids; hippocampus; rats.

FIGURE 1

Overview of placements of the injection needle tips within the dorsal hippocampus (A) and example photomicrograph illustrating placement of the needle tips in one rat (B). Large arrows point to the cannula tips, and small arrows point to the injection needle tips. Diagram is redrawn from Paxinos and Watson (2007).

FIGURE 2

(A) Object-place recognition task. During the sampling phase the rats were exposed to an open field arena with two identical objects. During the 80 min retention phase the animals were either allowed to sleep or were sleep deprived. In the sleep conditions, the animals were infused with corticosterone or vehicle once they showed first signs of sleep; in the wake conditions, timing of the infusion was matched to that of the sleep conditions. During the retrieval phase the position of one of the objects was changed and the time spent exploring the two objects was assessed. Increased exploration time for the displaced object indicates memory for the location of the nondisplaced object. (B) Novel-object recognition task. The design of this task was identical to the object-place recognition task except for the retrieval phase when one of the familiar objects was replaced by a novel object. (C) Corticosterone effect on consolidation of object-place recognition task in sleep and wakefulness. *P < 0.05 for difference between conditions, two-tailed, except for Sleep/Vehicle vs. Wake/Vehicle where directed one-tailed testing was used; F(1,29) = 11.09, P = 0.002, for sleep/wake × substance interaction; +P < 0.05 for significant difference from chance level. (D) There was no significant effect of sleep or intrahippocampal corticosterone infusion on novel-object recognition. Performance of all the groups during novel-object recognition test was above chance (+ for P < 0.05). Numbers in the bars indicate sample size (N).