Sleep-dependent surges in growth hormone do not contribute to sleep-dependent memory consolidation

Summary

In the search for the mechanisms that mediate the effects of sleep on the consolidation of memories, growth hormone (GH) recently became of interest, because in humans it is released mainly during slow-wave sleep (SWS), a period of enhanced declarative memory consolidation. In addition, recent studies showed that GH is involved in proper memory function in GH deficient and elderly humans and this effect has been linked to regulatory influences of GH on hippocampal NMDA receptors. Here, we blocked GH secretion by intravenous infusion of somatostatin in healthy young subjects during the first 3 h of sleep, which contain mainly SWS. Declarative and procedural memory consolidation was tested across this period, using a word pair association task and a mirror tracing task, respectively. Although GH was effectively suppressed, memory performance as well as sleep were entirely unaffected by this suppression. Whereas GH may in the long run generally support brain systems required for maintaining proper memory function, our data exclude a necessary contribution of the nocturnal surge in pituitary GH secretion to the acute processing and formation of specific memories during sleep.

Introduction

In recent years, a number of studies confirmed the notion that sleep enhances memory consolidation in both the declarative and the procedural memory systems (Gais and Born, 2004a, Walker and Stickgold, 2004). However, the mechanisms possibly mediating this function of sleep, like the various changes in brain activity and endocrine secretion, are still poorly understood. Most theories on how sleep improves memory consolidation come from animal studies, which investigated the neural brain electrical activity that presumably underlies information processing during sleep. The contribution of endocrine activity related to sleeping on the other hand, has not received much attention, although there are good reasons to assume that hormones are involved in modulating memory systems (Payne et al., 2005).

Neuroendocrine activity during sleep is very different from that of wakefulness. Hormone secretion and activity of neuromodulators change radically at the transition form wakefulness to sleep and between non-rapid eye movement (NREM) and REM sleep stages. Characteristic features of nocturnal slow-wave sleep (SWS) are the circadian nadir of cortisol secretion, the high release of growth hormone (GH) and the cessation of neuromodulatory cholinergic activity (Born and Fehm, 1998, Hasselmo, 1999). Some of these changes have already been implicated as mediators in the relationship between sleep and memory. The suppression of cortisol release during the first hours of nocturnal sleep was one of the first characteristics of sleep shown to enhance sleep related declarative memory consolidation (Plihal and Born, 1999). Lack of cholinergic modulatory activity during SWS, which supposedly switches the hippocampal memory system into a ‘replay’ mode (Hasselmo, 1999), also proved a necessary condition for declarative memory consolidation during sleep (Gais and Born, 2004b).

Growth hormone is a peptide hormone that is secreted principally from the anterior pituitary. Via hypothalamic inputs its release is mainly stimulated by GH-releasing hormone and inhibited by somatostatin. GH has been related in previous studies to sleep and to memory function. GH in adult humans is secreted mainly during the first part of nocturnal sleep in close association with the intense periods of SWS predominating this part of the night (Born and Fehm, 1998). This phase of sleep is also known to contribute to declarative memory consolidation (Plihal and Born, 1997). Several authors have proposed that GH is also involved in memory function, e.g. by inducing gene expression for glutamatergic NMDA receptors in the hippocampus, a process assumed to underlie declarative memory function (Nyberg, 2000, Le Greves et al., 2002). GH prevents neuronal loss in the hippocampus of old rats (Azcoitia et al., 2005), and, in patients with GH deficiency, replacement of GH leads to enhancement of short- and long-term declarative memory performance (Arwert et al., 2005). Together, such findings led Payne et al. (2005) to suggest that GH release during early SWS-rich sleep may contribute to the enhanced memory consolidation taking place during this part of sleep. The aim of the present study was to investigate this possible relationship between sleep-dependent GH secretion and memory consolidation during sleep. To achieve this aim, healthy subjects were administered intravenous somatostatin, which consistently suppresses GH secretion, but does not pass the blood–brain barrier and, thus, is not active centrally (Meisenberg and Simmons, 1983).