Hippocampal spine changes across the sleep-wake cycle: Corticosterone and kinases

Abstract

The corticosterone (CORT) level changes along the circadian rhythm. Hippocampus is sensitive toCORT, since glucocorticoidreceptors are highly expressed. Inrathippocampus fixedin a living state every 3 h, we found that the dendritic spine density of CA1 pyramidal neurons increased uponwaking(within 3 h), as comparedwiththe spine density in the sleep state. Particularly, the large-headspines increased.Theobservedchangeinthespinedensitymaybedueto the change in the hippocampal CORT level, since the CORT level at awake state (w30 nM) in cerebrospinal fluid was higher than that at sleep state (w3 nM), as observed from our earlier study. In adrenalectomized (ADX) rats, such a wake-induced increase of the spine density disappeared. S.c. administration of CORT intoADX rats rescued the decreased spine density. By using isolated hippocampal slices, we found that the application of 30 nM CORT increased the spine density within 1 h and that the spine increase was mediated via PKA, PKC, ERK MAPK, and LIMK signaling pathways. These findings suggest that the moderately rapid increase of the spine density on waking might mainly be caused by the CORT-driven kinase networks.