ORIGINAL ARTICLE Fast Effects of Glucocorticoids on Memory-Related Network Oscillations in the Mouse Hippocampus E. K. Weiss, N. Krupka, F. Ba ¨hner, M. Both and A. Draguhn Institut fu ¨ r Physiologie und Pathophysiologie, Universita ¨t Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany. Elevated concentrations of glucocorticoids interfere with the forma- tion and consolidation of declarative memories. For example, the blocking or deletion of 11b-hydroxysteroid reductase (an enzyme increasing active glucocorticoid isoforms in the brain) improves spatial memory in mice (1) and verbal memory in men (2). By con- trast, acute administration of glucocorticoids in humans during early sleep phases impairs memory (3). Similarly, memory dysfunc- tion is observed in clinical depression, which accompanies chroni- cally elevated levels of corticosteroids (4–6). A key area linking glucocorticoid signalling and declarative mem- ory is the hippocampal formation. The mammalian hippocampus expresses mineralocorticoid and glucocorticoid receptors at high density (7) and is involved in a negative feedback regulation of the stress response mediated by the hypothalamo-pituitary-adrenal (HPA) axis (5, 8). Animal models of chronic stress disorders or depression, as well as studies in humans, show structural changes in the hippocampus, including dendritic shrinkage, reduced neuro- genesis in the dentate gyrus and decreased hippocampal volume (9). These changes might account for the memory deficits described in patients with major depression (10). Moreover, aged humans with prolonged cortisol elevations display deficits in hippocampus- dependent memory tasks together with a reduced hippocampal vol- ume (11). Classically, steroid hormones act by binding to intracellularly located receptors which, after transition into the nucleus, alter the expression of multiple target genes. The subsequent effects on pro- tein expression and neuronal signalling can develop within < 1 h (12). In addition, there might even be faster, nongenomic steroid effects on cellular signalling (13–17). Together, there is good evi- dence for rapid effects of glucocorticoids on neuronal signalling and network functions which, in turn, might alter declarative, epi- sodic or spatial memory. We therefore analysed the effects of acutely elevated glucocorticoid levels on neuronal network func- tions in mouse hippocampal slices. Recent data indicate that acqui- sition of new information is accompanied by hippocampal gamma oscillations (usually superimposed on theta activity) (18). During slow-wave sleep, the predominant pattern of activity is character- ised by sharp wave-ripple complexes (SPW-R), which may be Journal of Neuroendocrinology Correspondence to: Andreas Draguhn, Institut fu ¨r Physiologie und Pathophysiologie, Universita ¨t Heidelberg, Im Neuenheimer Feld 326, 69120 Heidelberg Germany (e-mail: andreas.draguhn@ physiologie.uni-heidelberg.de). Transient or lasting increases in glucocorticoids accompany deficits in hippocampus-dependent memory formation. Recent data indicate that the formation and consolidation of declarative and spatial memory are mechanistically related to different patterns of hippocampal network oscillations. These include gamma oscillations during memory acquisition and the faster ripple oscillations (approximately 200 Hz) during subsequent memory consolidation. We therefore anal- ysed the effects of acutely applied glucocorticoids on network activity in mouse hippocampal slices. Evoked field population spikes and paired-pulse responses were largely unaltered by corti- costerone or cortisol, respectively, despite a slight increase in maximal population spike ampli- tude by 10 lM corticosterone. Several characteristics of sharp waves and superimposed ripple oscillations were affected by glucocorticoids, most prominently the frequency of spontaneously occurring sharp waves. At 0.1 lM, corticosterone increased this frequency, whereas maximal (10 lM) concentrations led to a reduction. In addition, gamma oscillations became slightly faster and less regular in the presence of high doses of corticosteroids. The present study describes acute effects of glucocorticoids on sharp wave-ripple complexes and gamma oscillations in mouse hippocampal slices, revealing a potential background for memory deficits in the presence of elevated levels of these hormones. Key words: glucocorticoids, stress, memory, hippocampus, network oscillations. doi: 10.1111/j.1365-2826.2008.01699.x Journal of Neuroendocrinology 20, 549–557 ª 2008 The Authors. Journal Compilation ª 2008 Blackwell Publishing Ltd