Sleep restriction suppresses neurogenesis induced by hippocampal learning

Stanford University, Palo Alto, California, United States
Journal of Neurophysiology (Impact Factor: 2.89). 01/2006; 94(6):4224-33. DOI: 10.1152/jn.00218.2005
Source: PubMed


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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    • "The observation that REM sleep is critical for the spatial learning in the Morris water maze has been confirmed by some laboratories (Youngblood et al. 1997; Guan et al. 2004; Yang et al. 2008; Li et al. 2009), but not by some others (Wang et al. 2009; Walsh et al. 2011). The apparent inconsistent findings on the consequences of sleep deprivation in the water maze may be explained by the fact that animals while undergoing training can adopt alternative behavioral learning strategies that are not necessarily dependent on the hippocampus (Bjorness et al. 2005; Hairston et al. 2005). Instead of locating the platform on the basis of the spatial cues in the testing room, animals may confer to using other strategies that do not rely on those cues. "
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    ABSTRACT: Although the exact functions of sleep remain a topic of debate, several hypotheses propose that sleep benefits neuronal plasticity, which ultimately supports brain function and cognition. For over a century, researchers have applied a wide variety of behavioral, electrophysiological, biochemical and molecular approaches to study how memory processes are promoted by sleep and perturbed by sleep loss. Interestingly, experimental studies indicate that cognitive impairments as a consequence of sleep deprivation appear to be most severe with learning and memory processes that require the hippocampus, which suggests that this brain region is particularly sensitive to the consequences of sleep loss. Moreover, recent studies in laboratory rodents indicate that sleep deprivation impairs hippocampal neuronal plasticity and memory processes by attenuating intracellular cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling. Attenuated cAMP-PKA signaling can lead to a reduced activity of the transcription factor cAMP response element binding protein (CREB) and ultimately affect the expression of genes and proteins involved in neuronal plasticity and memory formation. Pharmacogenetic experiments in mice show that memory deficits following sleep deprivation can be prevented by specifically boosting cAMP signaling in excitatory neurons of the hippocampus. Given the high incidence of sleep disturbance and sleep restriction in our 24/7 society, understanding the consequences of sleep loss and unraveling the underlying molecular mechanisms is of great importance.
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    • "But mainly the notion that sleep is associated with offline network remodeling, leading to memory retention, has led researchers to link EEG changes in sleep with behavioral plasticity. Indeed, some forms of learning have been found to influence SWA (e.g., Huber et al., 2008; Mascetti et al., 2013), spindle activity (Gais, Molle, Helms, & Born, 2002), and the amount of REM sleep (e.g., Hairston et al., 2005; Smith & Rose, 1997). It is today commonly assumed that experience-dependent neural plasticity during sleep is integral to global processes of memory consolidation. "
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    ABSTRACT: The main mystery about sleep is why we do not do more of it. Almost every type of human function or dysfunction involves sleep disruption, from our perception of sleep as an impediment to our social and professional lives, thus direct- ing our schedules to restrict the time we allocate for sleep; to psychiatric disorders, the majority of which interfere with sleep patterns. This is even more enigmatic consider- ing the overlap between sleep regulatory mechanisms and reward systems, as will be outlined here. Like the major- ity of psychiatric disorders, sleep disturbances are a central feature of addictions, with different substances associated with divergent effects on sleep regulation and subjective sleep quality. Clearly, the long- and short-term pharmaco- logical effects of a psychoactive drug alter the functional- ity of brain systems associated with arousal states; hence, it would be expected that continued use of such substances would impact sleep patterns. However, the links between the motivational effects of drug use and sleep are far more complex. I propose a model that will demonstrate that key mechanisms involved in the susceptibility to engage in drug-seeking behaviors and to develop an addiction are linked to sleep and sleep disruption. The emerging model suggests that the same systems that reinforce drug-seeking behaviors are also activated during sleep. As replay patterns during sleep have been linked to consolidation of memories, sleep, per se, may have a role in the creation of addiction. With this in mind, the proposed model may also provide a tentative answer to the questions posed, suggesting that sleep deprivation, at least in a mild form, is reinforcing.
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    • "Individuals with sleep disturbances often have altered LC function (Berridge et al. 2012), which may increase the likelihood of acquiring PTSD by predisposing the hippocampal–PFC– amygdala circuit to the effects of a traumatic event. In addition to the effects of NA at the CA1 inputs and in reducing PFC activity, disturbed sleep can also lead to reduced dentate gyrus volume through impaired neurogenesis (Guzman-Marin et al. 2003, 2005; Hairston et al. 2005). "
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    ABSTRACT: Post-traumatic stress disorder (PTSD) is characterized by intrusive memories of a traumatic event, avoidance behavior related to cues of the trauma, emotional numbing, and hyper-arousal. Sleep abnormalities and nightmares are core symptoms of this disorder. In this review, we propose a model which implicates abnormal activity in the locus coeruleus (LC), an important modifier of sleep-wake regulation, as the source of sleep abnormalities and memory abnormalities seen in PTSD. Abnormal LC activity may be playing a key role in symptom formation in PTSD via sleep dysregulation and suppression of hippocampal bidirectional plasticity.
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Ilana S Hairston