Sleep Restriction Suppresses Neurogenesis Induced by Hippocampus-Dependent Learning

Abstract

Sleep deprivation impairs hippocampal-dependent learning, which, in turn, is associated with increased survival of newborn cells in the hippocampus. We tested whether the deleterious effects of sleep restriction on hippocampus-dependent memory were associated with reduced cell survival in the hippocampus. We show that sleep restriction impaired hippocampus-dependent learning and abolished learning-induced neurogenesis. Animals were trained in a water maze on either a spatial learning (hippocampus-dependent) task or a nonspatial (hippocampus-independent) task for 4 days. Sleep-restricted animals were kept awake for one-half of their rest phase on each of the training days. Consistent with previous reports, animals trained on the hippocampus-dependent task expressed increased survival of newborn cells in comparison with animals trained on the hippocampus-independent task. This increase was abolished by sleep restriction that caused overall reduced cell survival in all animals. Sleep restriction also selectively impaired spatial learning while performance in the nonspatial task was, surprisingly, improved. Further analysis showed that in both training groups fully rested animals applied a spatial strategy irrespective of task requirements; this strategy interfered with performance in the nonspatial task. Conversely, in sleep-restricted animals, this preferred spatial strategy was eliminated, favoring the use of nonspatial information, and hence improving performance in the nonspatial task. These findings suggest that sleep loss altered behavioral strategies to those that do not depend on the hippocampus, concomitantly reversing the neurogenic effects of hippocampus-dependent learning.

Neurogenesis and the spacing effect: Learning over time enhances memory and the survival of new neurons

“…This may be a result of procedural differences, including the age of the animals, the housing conditions, or antibody used for BrdU detection. However, the findings are generally consistent with our previous study and others as well (Dobrossy et al 2003;Drapeau et al 2003;Hairston et al 2005;Kee et al 2007). One study did report a reduction in cell number after spatial training (Mohapel et al 2006), but they used multiple injections of BrdU, making it difficult to assess how many cells are generated versus how many survive after training.…”

“…Therefore, the increase in cell survival was not induced by motor activity or the stress of the training procedure. Since the initial report, this phenomenon and related ones have been reported (Kempermann and Gage 2002;Dobrossy et al 2003;Drapeau et al 2003;Hairston et al 2005;Kee et al 2007). …”

“…Many studies have suggested that sleep, or even a brief period of rest, is important for consolidation to occur (Karni et al 1994) as well as for the spacing effect to emerge (Hintzman 1974). Interestingly enough, Hairston et al (2005) reported that spatial learning enhanced cell survival, but not if animals were deprived of sleep in between days of training. Similarly, in our studies, animals that were trained with massed trials had minimal opportunity to sleep.…”

Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids

“…Common targets of both stress and sleep deprivation include various growth factors (35)(36)(37)(38). Adult neurogenesis is known to be regulated by such extracellular signals (39), although the potential protracted effects of stress or sleep deprivation on neurotrophic levels have not been well characterized.…”

Is there a link between adult neurogenesis and learning?

“…However, the direction of the effect is not always the same. For example, it has been shown that training with trace eyeblink conditioning, spatial learning in the Morris water maze and conditioned food preference increase the number of newborn cells in the DG of adult rats (Gould et al, 1999c;Ambrogini et al, 2000;Lemaire et al, 2000;Dobrossy et al, 2003;Leuner et al, 2004c;Hairston et al, 2005;Olariu et al, 2005). These effects appear to be specific to learning that requires the hippocampus.…”