Brain activity intensity drives need for sleep
September 16, 2019
Science Daily/University College London
The intensity of brain activity during the day, notwithstanding how long we've been awake, appears to increase our need for sleep, according to a new UCL study in zebrafish.
The research, published in Neuron, found a gene that responds to brain activity in order to coordinate the need for sleep. It helps shed new light on how sleep is regulated in the brain.
"There are two systems regulating sleep: the circadian and homeostatic systems. We understand the circadian system pretty well -- our built-in 24-hour clock that times our biological rhythms, including sleep cycles, and we know where in the brain this rhythm is generated," explained lead author Dr Jason Rihel (UCL Cell & Developmental Biology).
"But the homeostatic system, which causes us to feel increasingly tired after a very long day or sleepless night, is not well understood. What we've found is that it appears to be driven not just by how long you've been awake for, but how intensive your brain activity has been since you last slept."
To understand what processes in the brain drive homeostatic sleep regulation -- independent of time of day -- the research team studied zebrafish larvae.
Zebrafish are commonly used in biomedical research, partly due to their near-transparent bodies that facilitate imaging, in addition to similarities to humans such as sleeping every night.
The researchers facilitated an increase in brain activity of the zebrafish using various stimulants including caffeine.
Those zebrafish which had drug-induced increased brain activity slept for longer after the drugs had worn off, confirming that the increase in brain activity contributed to a greater need for sleep.
The researchers found that one specific area of the zebrafish brain was central to the effect on sleep pressure: a brain area that is comparable to a human brain area found in the hypothalamus, known to be active during sleep. In the zebrafish brain area, one specific brain signalling molecule called galanin was particularly active during recovery sleep, but did not play as big a role in regular overnight sleep.
To confirm that the drug-induced findings were relevant to actual sleep deprivation, the researchers conducted a test where they kept the young zebrafish awake all night on a 'treadmill' where the fish were shown moving stripes -- by imitating fast-flowing water, this gives the fish the impression that they need to keep swimming. The zebrafish that were kept awake slept more the next day, and their brains showed an increase in galanin activity during recovery sleep.
The findings suggest that galanin neurons may be tracking total brain activity, but further research is needed to clarify how they detect what's going on across the whole brain.
The researchers say their finding that excess brain activity can increase the need for sleep might explain why people often feel exhausted after a seizure.
"Our findings may also shed light on how some animals can avoid sleep under certain conditions such as starvation or mating season -- it may be that their brains are able to minimise brain activity to limit the need for sleep," said the study's first author, Dr Sabine Reichert (UCL Cell & Developmental Biology).
The researchers say that by discovering a gene that plays a central role in homeostatic sleep regulation, their findings may help to understand sleep disorders and conditions that impair sleep, such as Alzheimer's disease.
"We may have identified a good drug target for sleep disorders, as it may be possible to develop therapies that act on galanin," added Dr Reichert.
https://www.sciencedaily.com/releases/2019/09/190916110556.htm
Sleep history predicts late-life Alzheimer's pathology
Findings suggest novel, sleep-based diagnosis and treatment methods
June 18, 2019
Science Daily/Society for Neuroscience
Sleep patterns can predict the accumulation of Alzheimer's pathology proteins later in life, according to a new study of older men and women published in JNeurosci. These findings could lead to new sleep-based early diagnosis and prevention measures in the treatment of Alzheimer's disease.
Alzheimer's disease is associated with disrupted sleep and the accumulation of tau and proteins in the brain, which can emerge long before characteristic memory impairments appear. Two types of hippocampal sleep waves, slow oscillations and sleep spindles, are synced in young individuals, but have been shown to become uncoordinated in old age.
Matthew Walker, Joseph Winer, and colleagues at the University of California, Berkeley found a decrease in slow oscillations/sleep spindle synchronization was associated with higher tau, while reduced slow-wave-activity amplitude was associated with higher ?-amyloid levels.
The researchers also found that a decrease in sleep quantity throughout aging, from the 50s through 70s, was associated with higher levels of ?-amyloid and tau later in life. This means that changes in brain activity during sleep and sleep quantity during these time frames could serve as a warning sign for Alzheimer's disease, allowing for early preventive care.
https://www.sciencedaily.com/releases/2019/06/190618102725.htm
Neural sleep patterns emerged at least 450 million years ago
July 10, 2019
Science Daily/Stanford Medicine
Researchers at the Stanford University School of Medicine have found that neural signatures in sleeping zebrafish are analogous to those of humans, suggesting that the brain activity evolved at least 450 million years ago, before any creatures crawled out of the ocean.
Scientists have known for more than 100 years that fish enter a sleeplike state, but until now they didn't know if their sleep resembled that of land animals.
The researchers found that when zebrafish sleep, they can display two states that are similar to those found in mammals, reptiles and birds: slow-wave sleep and paradoxical, or rapid eye movement, sleep. The discovery marks the first time these brain patterns have been recorded in fish.
"This moves the evolution of neural signatures of sleep back quite a few years," said postdoctoral scholar Louis Leung, PhD.
A paper describing the research will be published July 10 in Nature. Philippe Mourrain, PhD, associate professor of psychiatry and behavioral sciences, is the senior author. Leung is the lead author.
To study the zebrafish, common aquarium dwellers also known as danios, the researchers built a benchtop fluorescent light-sheet microscope capable of full-fish-body imaging with single-cell resolution. They recorded brain activity while the fish slept in an agar solution that immobilized them. They also observed the heart rate, eye movement and muscle tone of the sleeping fish using a fluorescence-based polysomnography that they developed.
They named the sleep states they observed "slow-bursting sleep," which is analogous to slow-wave sleep, and "propagating-wave sleep," analogous to REM sleep. Though the fish don't move their eyes during REM sleep, the brain and muscle signatures are similar. (Fish also don't close their eyes when they sleep, as they have no eyelids.)
Sleeping like the fish
The researchers found another similarity between fish and human sleep. By genetically disrupting the function of melanin-concentrating hormone, a peptide that governs the sleep-wake cycle, and observing neural expressions as the fish slept, the researchers determined that the hormone's signaling regulates the fish's propagating wave sleep the way it regulates REM sleep in mammals.
Other aspects of their sleep state are similar to those of land vertebrates, Mourrain said: The fish remain still, their muscles relax, their cardio-respiratory rhythms slow down and they fail to react when they're approached.
"They lose muscle tone, their heartbeat drops, they don't respond to stimuli -- the only real difference is a lack of rapid eye movement during REM sleep," Mourrain said, though he added, "The rapid movement of the eyes is not a good criterion of this state, and we prefer to call it paradoxical sleep, as the brain looks awake while one is asleep."
While scientists can't say for certain that all animals sleep, it appears to be a universal need among vertebrates and invertebrates. Animals will die if they are deprived of sleep long enough, and people who fail to receive adequate sleep suffer from mental problems such as memory lapses and impaired judgment, along with a higher risk of disorders such as obesity and high blood pressure.
The exact benefits of sleep are still a mystery, however. "It's an essential function," Mourrain said, "but we don't know precisely what it does."
He added that sleep disorders are linked to most neurological disorders such as autism spectrum disorders, Fragile X syndrome, and Alzheimer's and Parkinson's disease. "Sleep disturbances are an aggravating factor of these disorders," Mourrain said. It is critical to develop this animal model to study sleep functions at the cellular level, including neuronal connectivity and DNA repair, and in turn understand the pathophysiological consequences of sleep disruptions, he added.
The discovery means sleep research can be conducted on zebrafish, which are easy to study, in part because they're transparent. They breed quickly, are inexpensive to care for and are just over an inch long. Drug testing requires only the addition of chemicals to their water.
"Because the fish neural signatures are in essence the same as ours, we can use information about them to generate new leads for drug trials," Leung said. He added that mice, often a stand-in for human research, are nocturnal and a less relevant model for our sleep.
"As zebrafish are diurnal like humans, it's perhaps more biologically accurate to compare fish sleep with humans' for some aspects," Leung said.
https://www.sciencedaily.com/releases/2019/07/190710132015.htm