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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.

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