There is much research that supports the idea that sleep is necessary for memory consolidation: In a BBC News online article from February 2007, research is presented that concerns the damage that lack of sleep can have on the brain: Researchers at Princeton University found that a lack of sleep affected the hippocampus in rats. This is important because the hippocampus is the region in the brain primarily involved with memory. Rats who were sleep deprived for 72 hours were compared with rats who had normal sleep. The sleep-deprived rats had higher levels of corticosterone, which is the stress hormone. There were also less new brain cells found in the deprived rats. The article hypothesized that sleep deprivation caused the release of more stress hormone and that this stress hormone reduced cell growth. The researchers also said that this lack of new cells probably has something to do with the cognitive defecits involved in sleep deprivation. "No sleep means no new brain cells." http://news.bbc.co.uk/2/hi/health/6347043.stm ***The following information comes from a paper that I wrote summarizing 3 journal articles on the topic of how long term potentiation affects memory consolidation during sleep (the paper was for a Cellular and Molecular Neurobiology class, December 2008): A lot of the current research on this topic looks at how sleep deprivation affects long-term potentiation [LTP] in the brain, and thus affects memory consolidation as well (LTP is the main molecule responsible for changing synapses and storing memory). Long-term potentiation occurs by changing the synapses in the brain and adding additional AMPA receptors. These changes last a long time (Nicholls et al. 2001). Many researchers are finding that sleep deprivation (especially involving REM sleep) has a negative effect on LTP formation, which in turn retards memory formation in the brain. When the brain is awake, memories and information reach the hippocampus through the entorhinal cortex. Yet when the brain is asleep, information is transferred from the hippocampus to the neocortex. It is hypothesized that this reverse transfer of information during sleep takes place correctly because of the regular wake-sleep cycle that the body undergoes. These bursts of information are initiated during slow wave sleep and affect synaptic plasticity (Buzsaki 1998). Another review suggests that sleep and LTP are linked. Stimulation produced LTP in the dentate gyrus during REM sleep. Stimulation during post-learning REM sleep also produced LTP. Studies were also done using classical conditioning during REM sleep, and it was found that classical conditioning could be restored upon presentation of the conditioned stimulus. Associative learning could be induced during REM sleep as well. Thus much of the information acquired while one is awake is also available during sleep (Benington and Frank 2003). Sleep deprivation, especially REM sleep deprivation, has a negative effect on LTP formation and thus impairs memory consolidation in the brain. Recent research confirms these negative effects. Much of this research involves sleep-depriving rats and looking at how this affects LTP formation in hippocampal neurons. Some research is also done directly on humans. In the animal model research done, rats are typically used. The rats are placed in standard conditions (home cages, controlled environment, and regular cycles). Then some of the animals are sleep deprived. Sleep deprivation can be induced in several different ways. Some researchers sleep deprived the rats using a rotating drum (Campbell, Guinan, and Horowitz 2002). Others induced sleep deprivation by gentle handling of the recording chamber (Romcy-Pereira and Pavlides 2004). Another technique was single small platform sleep deprivation (McDermott et al.). After sleep deprivation was induced, the researchers used various techniques to analyze the effects that it had on the brains of the rats. Recording corticosterone levels was a relatively common procedural technique. Hippocampal slicing was a good way to look at the effects of sleep deprivation as well. After sleep deprivation, the rat brains were removed and chilled. The Schaffer collaterals were stimulated so that spikes from the CA1 region of the hippocampus could be recorded. LTP was also induced. (Campbell, Guinan, and Horowitz 2002). Another group of researchers implanted electrodes so that EEGs of the animals during sleep could be recorded before, during, and after sleep deprivation. They also induced LTP to characterize its decay pattern and look at the responses (Romcy-Pereira and Pavlides 2004). McDermott et al. (2003) used a combination of both slicing and EEG techniques to compile their data. EEG recordings were used to determine the level and type of sleep deprivation via electrodes implanted into various areas of the rat brains. After deprivation, contextual versus cued memory tests were performed by placing the rats in an operant conditioning chamber and conditioning freezing behavior. Slices from the hippocampus were also taken and whole-cell recording was used. LTP was once again induced into the Schaffer collaterals and recorded. All of these rat studies used similar procedures to sleep deprive the rats and look at the effects of this deprivation. However, another study that looks at the same thing used humans instead of the animal model to look at how sleep and memory formation are intertwined. Human subjects were assigned to either a normal sleep (control) group or a sleep-deprived (experimental) group. All subjects were subjected to an episodic memory encoding session while being scanned with a functional MRI. The sleep-deprived subjects had 35 hours of sleep deprivation before the encoding session, while the control group had normal sleep. Two days later, all subjects returned for a recognition test, this time without the fMRI. Results of the recognition tests as well as the original fMRIs were used to look at the changes induced by sleep deprivation. This study is in many ways more relevant because it uses humans; however, the effects of sleep deprivation at the molecular level can only be speculated (Yoo et al. 2007). The results of the three rat studies discussed as well as the human study all support the idea that sleep deprivation does indeed impair memory consolidation. The first experiment discussed that used a rotating drum and hippocampal slices from rats found that LTP was impaired in the sleep-deprived rats. The average potentiation in control rats was significantly larger than in sleep deprived rats. This reduced plasticity was recorded from the hippocampal slices. The researchers believe that this reduction may be at the root of various cognitive impairments induced by sleep deprivation. They also hypothesize that this reduced plasticity from sleep deprivation can impair various physiological processes, such as learning, memory consolidation, and cognitive performance. Testing the corticosterone levels of the rats also produced significant results. Elevated levels were in the sleep-deprived rats, suggesting that the stress response induced by sleep deprivation may have also contributed to the decline of LTP (Campbell, Guinan, and Horowitz 2002). Another experiment also resulted in similar conclusions. Rats were implanted with electrodes to record EEGs of all sleep states. Animals that were sleep deprived spent less time in all sleep states. LTP spikes were also recorded from rats under all conditions (completely sleep-deprived, REM sleep-deprived, and normal). A faster decay of LTP in the dentate gyrus was seen in sleep deprived groups in comparison with the normal animals. However, LTP was prolonged in the medial prefrontal cortex in REM sleep-deprived rats. This showed that the specific physiological state that REM sleep induces is important in synaptic plasticity (Romcy-Pereira and Pavlides 2004). Other researchers found a similar decline in LTP from sleep deprivation. Sleep stages were recorded using electrodes, and LTP was once again induced. Memory formation was also tested via operant conditioning of freezing behavior, as mentioned before. Researchers found that 88% less freezing occurred in sleep-deprived (72 hour sleep deprivation) rats. Cellular recording showed that in sleep-deprived rats, half the number of spikes were produced compared to rats that had a normal amount of sleep. Also, the magnitude of LTP induced in the CA1 pyramidal neurons and the dentate gyrus (DG) granule cells was reduced in the slices of sleep-deprived rats. Researchers hypothesize that this decrease in LTP inhibits memory and could also be responsible for decaying the encoding of spatial information (McDermott et al. 2003). All of these experiments involving LTP in rats showed that sleep deprivation does indeed have negative affects on LTP in rats, and thus more than likely affects memory consolidation. The experiment done on humans also demonstrated the negative cognitive effects of sleep deprivation. Performance on the recognition test described before was much poorer in sleep-deprived subjects, thus the researchers concluded that sleep deprivation impairs coding ability. The functional MRIs also showed some significant differences. There was decreased activation in the bilateral posterior hippocampal regions of sleep-deprived subjects. This experiment shows that even in human subjects, sleep deprivation causes significant impairments (Yoo et al. 2007). Through all of these experiments, both rat and human, it is easy to see how sleep deprivation impairs various processes in the brain, particularly those involved in LTP formation. LTP formation was significantly delayed or impaired in all sleep deprived rats and sleep-deprived rats also showed performance deficits on cognitive tests. Sleep-deprived humans showed memory deficits as well as decreased activation in certain areas of the brain, necessitating some sort of molecular factor as the cause for this. Thus it can be observed that sleep deprivation impairs memory formation, presumably via impairing the formation of LTP, which is the basis of memory and changing synapses in all organisms. This research supports the idea that sleep is an important part of memory consolidation. References: Benington, J. H. and M. G. Frank. 2003. Cellular and molecular connections between sleep and synaptic plasticity. Progress in Neurobiology, 69: 71-101. Buzsaki, G. 1998. Memory consolidation during sleep: A neurophysiological perspective. Journal of Sleep Research, 7 (1): 17-23. Campbell, I. G.,
Guinan, M. J., and J. M. Horowitz.
2002. Sleep deprivation impairs
long-term potentiation in rat hippocampal slices. Journal of Neurophysiology, 88: 1073-1076. McDermott, C. M., LaHoste, G. J., Chen, C., Musto, A., Bazan, N. G., and J. C. Magee. 2003. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. The Journal of Neuroscience, 23 (29): 9687-9695. Nicholls, J. G., A. R. Martin, B. G. Wallace, and P. A. Fuchs. 2001. From Neuron to Brain. 4th edition. Sinauer Associates, Inc. Romcy-Pereira, R. and C. Pavlides. 2004. Distinct modulatory effects of sleep on the maintenance of hippocampal and medial prefrontal cortex LTP. European Journal of Neuroscience, 20: 3453-3462. Yoo, S., Hu, P.
T., Gujar, N., Jolesz, F. A., and M. P. Walker.
2007. A deficit in the ability to
form new human memories without sleep.
Nature Neuroscience, 10 (3):
385-392. |