Bats, birds, box turtles, humans and many other animals share at least one thing in common: They sleep. Humans, in fact, spend roughly one-third of their lives asleep, but sleep researchers still don’t know why.

According to the journal Science, the function of sleep is one of the 125 greatest unsolved mysteries in science. Theories range from brain “maintenance” - including memory consolidation and pruning - to reversing damage from oxidative stress suffered while awake, to promoting longevity. None of these theories are well established, and many are mutually exclusive.

Now, a new analysis by Jerome Siegel, UCLA professor of psychiatry and director of the Center for Sleep Research at the Semel Institute for Neuroscience and Human Behavior at UCLA and the Sepulveda Veterans Affairs Medical Center, has concluded that sleep’s primary function is to increase animals’ efficiency and minimize their risk by regulating the duration and timing of their behavior.

The research appears in the current online edition of the journal Nature Reviews Neuroscience.

“Sleep has normally been viewed as something negative for survival because sleeping animals may be vulnerable to predation and they can’t perform the behaviors that ensure survival,” Siegel said. These behaviors include eating, procreating, caring for family members, monitoring the environment for danger and scouting for prey.

“So it’s been thought that sleep must serve some as-yet unidentified physiological or neural function that can’t be accomplished when animals are awake,” he said.

Siegel’s lab conducted a new survey of the sleep times of a broad range of animals, examining everything from the platypus and the walrus to the echidna, a small, burrowing, egg-laying mammal covered in spines. The researchers concluded that sleep itself is highly adaptive, much like the inactive states seen in a wide range of species, starting with plants and simple microorganisms; these species have dormant states - as opposed to sleep - even though in many cases they do not have nervous systems. That challenges the idea that sleep is for the brain, said Siegel.

“We see sleep as lying on a continuum that ranges from these dormant states like torpor and hibernation, on to periods of continuous activity without any sleep, such as during migration, where birds can fly for days on end without stopping,” he said.

Hibernation is one example of an activity that regulates behavior for survival. A small animal, Siegel noted, can’t migrate to a warmer climate in winter. So it hibernates, effectively cutting its energy consumption and thus its need for food, remaining secure from predators by burrowing underground.

Sleep duration, then, is determined in each species by the time requirements of eating, the cost-benefit relations between activity and risk, migration needs, care of young, and other factors. However, unlike hibernation and torpor, Siegel said, sleep is rapidly reversible - that is, animals can wake up quickly, a unique mammalian adaptation that allows for a relatively quick response to sensory signals.

Humans fit into this analysis as well. What is most remarkable about sleep, according to Siegel, is not the unresponsiveness or vulnerability it creates but rather that ability to reduce body and brain metabolism while still allowing that high level of responsiveness to the environment.

“The often cited example is that of a parent arousing at a baby’s whimper but sleeping through a thunderstorm,” he said. “That dramatizes the ability of the sleeping human brain to continuously process sensory signals and trigger complete awakening to significant stimuli within a few hundred milliseconds.”

In humans, the brain constitutes, on average, just 2 percent of total body weight but consumes 20 percent of the energy used during quiet waking, so these savings have considerable adaptive significance. Besides conserving energy, sleep invokes survival benefits for humans too - “for example,” said Siegel, “a reduced risk of injury, reduced resource consumption and, from an evolutionary standpoint, reduced risk of detection by predators.”

“This Darwinian perspective can explain age-related changes in human sleep patterns as well,” he said. “We sleep more deeply when we are young, because we have a high metabolic rate that is greatly reduced during sleep, but also because there are people to protect us. Our sleep patterns change when we are older, though, because that metabolic rate reduces and we are now the ones doing the alerting and protecting from dangers.”

The Center for Sleep Research is part of the Semel Institute for Neuroscience and Human Behavior at UCLA, an interdisciplinary research and education institute devoted to the understanding of complex human behavior, including the genetic, biological, behavioral and sociocultural underpinnings of normal behavior, and the causes and consequences of neuropsychiatric disorders.

Source:
Mark Wheeler

University of California - Los Angeles

Experts have long suspected that part of the process of turning fleeting short-term memories into lasting long-term memories occurs during sleep. Now, researchers at the RIKEN-MIT Center for Neural Circuit Genetics of MIT’s Picower Institute for Learning and Memory have shown that mice prevented from “replaying” their waking experiences while asleep do not remember them as well as mice who are able to perform this function.

The work, which has a profound implication in the century-old search for the purpose of sleep, will be reported in the June 25 issue of Neuron.

It is widely believed that memories of events and spaces are stored briefly in the hippocampus before they are consolidated in the neocortex for permanent storage. The seahorse-shaped hippocampus is thought to play a key role in learning and memory, but the precise circuits and mechanisms involved are not well understood.

“Our work demonstrates the molecular link between post-experience sleep and the establishment of long-term memory of that experience,” said Susumu Tonegawa, the Picower Professor of Biology and Neuroscience at MIT and lead author of the study. “Ours is the first study to demonstrate this link between memory replay and memory consolidation. The sleeping brain must replay experiences like video clips before they are transformed from short-term into long-term memories.”

The researchers looked at a circuit within the hippocampus known as the trisynaptic pathway, in which neuronal information passes through the hippocampus’ three main substructures before moving on. “We demonstrated that this pathway is crucial for the transformation of a recent memory, formed within a day, to a remote memory that still exists at least six weeks later,” Tonegawa said.

Creating a strain of engineered mice in which a change of diet shuts down trisynaptic circuits, the researchers implanted electrodes that monitored the activities of the animals’ hippocampal cells as the animals ran a maze and then slept.

Not-so-instant replay

While they were still awake and running, the mice formed within their brains a pattern of place cells, or neurons that were firing in recognition of the maze the mice had learned to negotiate. During their post-run sleep, particularly during a deep sleep phase called slow-wave, the specific sequence of place cells that fired during the run was “replayed” in a similar sequence.

In human studies testing the role of slow-wave sleep in memory consolidation, the group that napped after memorizing word pairs such as “fruit-banana” and “tool-pliers,” was able to recall a greater number of word pairs than those who did not nap.

This replay during sleep had been speculated, but has never been demonstrated, to be important for converting the recent memory stored in the hippocampus to a more permanent memory stored in the neocortex. “We have demonstrated that in the mutant mice in which the trisynaptic pathway is blocked, this replay process during the slow-wave sleep is impaired,” Tonegawa said. The animals were able to form long-term memories of the maze only when their trisynaptic pathways were functioning after the formation of the short-term memory.

“Our conclusion is that the trisynaptic pathway-mediated replay of the hippocampal memory sequence during sleep plays a crucial role in the formation of a long-term memory,” he said.

In addition to Tonegawa, authors are Picower Institute research scientist Toshiaki Nakashiba, Picower Institute postdoctoral associate Derek L. Buhl and Picower Institute research scientist Thomas J. McHugh.

This work was supported by the National Institutes of Health and Otsuka Pharmaceutical Development & Commercialization Inc. based in Tokyo.

Written by Deborah Halber, Picower Institute

Source
MIT