Posts Tagged ‘ sleep ’

Wakefulness Cells

Certain groups of neurons determine whether light keeps us awake or not, says a new study.

Just a typical day for a hypocretin-deficient mouse. Okay, I'll wait for you to finish making that squinchy "Awww!" face, and then we'll move on with the article.

In the hypothalamus – a brain structure responsible for regulating hormone levels – specific kinds of neurons release a hormone called hypocretin (also known as hcrt or orexin). Hypocretin lets light-sensitive cells in other parts of the brain – such as the visual pathway – know that they should respond to incoming light by passing along signals for us to stay awake.

Scientists have understood for centuries that most animals and plants go through regular cycles of wakefulness and sleep – they call these patterns circadian rhythms or circadian cycles. More recently, researchers have begun unraveling the various chemical messaging systems our bodies use to time and control these cycles – enzymes like PER and JARID1a, which help give us an intuitive sense of how long we’ve been awake or asleep.

But now, as the Journal of Neuroscience reports, a team led by UCLA’s Jerome Siegel has isolated a neurochemical messaging system that dictates whether or not we can stay awake during the day at all. The team bred a special strain of mice whose brains were unable to produce hypocretin, and found that these mice acted like students in first-period algebra – even under bright lights, they just kept dozing off. However, they did jump awake when they received a mild electric shock:

This is the first demonstration of such specificity of arousal system function and has implications for understanding the motivational and circadian consequences of arousal system dysfunction.

What’s even more interesting, though, is that there’s a second half to this story – the dozy mice were perfectly perky in the dark:

We found that Hcrt knock-out mice were unable to work for food or water reward during the light phase. However, they were unimpaired relative to wild-type (WT) mice when working for reward during the dark phase or when working to avoid shock in the light or dark phase.

In other words, the mice without hypocretin stayed awake and worked for food just fine when the lights were out. So they probably have promising futures as bartenders or bouncers.

The takeaway here is that hypocretin isn’t so much responsible for enabling knee-jerk reactions as it is for helping mice (and us) stay alert and motivated to complete reward-based tasks when the lights are on. Without this hormone, we might act normally at night, but we just wouldn’t feel like staying awake when the sun was out.

And that’s exactly what Siegel’s team had found in several of their earlier studies, which linked human hypocretin deficiency with narcolepsy – a disease that causes excessive sleepiness and frequent daytime “sleep attacks.” These new results suggest that narcoleptic patients might have more success getting work done during the night, when their symptoms might be less severe.

Siegel also thinks clinically administered hypocretin might help block many effects of depression, and allow depressed patients to feel more motivated to get up and about during the day. If so, this could be a promising new form of treatment for that disease as well.

Finally, and perhaps most intriguingly of all, it’s likely that similar hormonal response “gateways” play crucial roles in other neurochemical arousal systems – like those involved in fearanger, and sexual excitement. If so, discoveries along those lines could provide us with some staggering new insights into the ways our brains regulate their own behavior.

So, I know what you’re probably wondering: am I really advocating the use of electric shocks to keep bored math students awake? Of course not – I think releasing wild badgers into the classroom would be much more effective.

Brain Scans & Lucid Dreams

The brain activity of lucid dreamers – people who become aware that they’re in a dream state – shows some interesting similarities with that of people who are awake, says a new study.

"Ahh - nothing puts me to sleep like a roomful of bright lights!"

By studying the brain activity of lucid dreamers under electroencephalograms (EEGs) and fMRI scans, researchers have found that activity in the somatosensory and motor cortices – regions crucial for touch and movement, respectively – show very similar activation patterns during lucid dreams to those they display when people make or imagine those same movements while awake.

Though dreams have fascinated philosophers and scientists since the dawn of history – some of the earliest written texts are dream-interpretation handbooks from ancient Egypt and Babylon – it’s only in recent years that neuroscience has begun to advance the study of dreams beyond Freudian theorizing and into the realm of hard data.

In the early 1950s, scientists identified several stages of sleep, including rapid eye movement (REM) sleep – the stage in which dreaming takes place; and in 1959, a team discovered a certain class of brain waves – ponto-geniculo-occipital (PGO) waves – which only appear during REM sleep.

Then, in 2009, an EEG study found that lucid dreams exhibit slightly different wave patterns from those associated with ordinary REM sleep – and later that year, another study proposed an astonishing theory: that REM sleep might be a form of proto-consciousness, which performs maintenance and support duty for the “full” consciousness that took over for it at some point in our evolution.

Now, as the journal Current Biology reports, a team led by Michael Czisch at Germany’s Max Planck Institute has made a new leap forward in dream research. By concentrating their research on lucid dreams, the team were able to map the neural correlates of controlled and remembered dream content:

Lucid dreamers were asked to become aware of their dream while sleeping in a magnetic resonance scanner and to report this “lucid” state to the researchers by means of eye movements. They were then asked to voluntarily “dream” that they were repeatedly clenching first their right fist and then their left one for ten seconds.

This approach has provided some surprising new insights into the ways our brains function in a dream state. By having the subjects retell their lucid dreams, the researchers were able to correlate recorded activation patterns with specific actions the subjects had “performed” while asleep:

A region in the sensorimotor cortex of the brain, which is responsible for the execution of movements, was actually activated during the dream. This is directly comparable with the brain activity that arises when the hand is moved while the person is awake. Even if the lucid dreamer just imagines the hand movement while awake, the sensorimotor cortex reacts in a similar way.

This confirms that the brain’s sensorimotor areas are actively involved in planning and executing movements in dreams, rather than just passively observing events.

What’s even more exciting is that, in light of other new technologies like the thought-video recorder, it looks like we may be able to record and play back our thoughts and dreams within the next few decades.

I think this research reflects an even more fundamental shift in thinking about neuroscience, though: as we unravel more and more of the neural correlates of phenomena like sleep and consciousness, we’re coming to realize just how vast a chasm yawns between scientific data and subjective experience.

Before long, it’s going to become essential for scanners and volunteers to be involved in the same continuous feedback loop – one in which the subjects can watch, in real time, the neural correlates of their thoughts and feelings from moment to moment, and adjust them accordingly to produce useful results.

Ambitious? I guess so. But a guy’s gotta have a dream.

Enzyme Alarm Clock

Researchers have isolated a protein that sounds our biological clock’s alarm each morning, a new study reports.

Energy-saving tip: try replacing your alarm clock with a live rooster!

A gene known as KDM5A codes for an enzyme (i.e., a protein that increases the rate of a chemical reaction) called JARID1a. This enzyme acts as a switch that starts the biochemical process of waking us from sleep – like some kind of weird molecular rooster.

Here’s the background: scientists have known for years that levels of a protein called PER rise in the morning and fall toward nighttime. The level of PER in our bodies helps our cells know what time of day it is – higher levels tell us it’s time to be awake, while lower levels help make us sleepy. This wake/sleep process is known as the circadian rhythm or circadian cycle.

Two genes – known as CLOCK and BMAL1 – help raise levels of PER. When those levels reach a certain critical point in the evening, CLOCK and BMAL1 stop triggering a rise in PER levels – and as those levels drop, our heart rate, blood pressure, and mental activity slow down in preparation for bedtime.

But this research marks a new discovery: a specific enzyme that restarts the circadian cycle in the morning, telling CLOCK and BMAL1 to start raising PER levels again.

As the journal Science reports, a team led by Satchindananda Panda at Salk’s Regulatory Biology Laboratory collaborated with teams at McGill University and Albert Einstein College of Medicine to discover JARID1a’s role in the circadian cycle. The teams genetically engineered fruit flies to under-produce JARID1a, and these flies seemed to have no idea what time of day it was – they woke and slept at random hours, and took naps throughout the day… much like college students.

Human and mouse cells engineered to produce less JARID1a also produced odd levels of PER:

JARID1a increased histone acetylation by inhibiting histone deacetylase 1 function and enhanced transcription by CLOCK-BMAL1 in a demethylase-independent manner. Depletion of JARID1a in mammalian cells reduced Per promoter histone acetylation, dampened expression of canonical circadian genes, and shortened the period of circadian rhythms.

In other words, less JARID1a led to shorter circadian cycles of PER production in the cells.

But wait – there’s more! Panda and his team also discovered that JARID1a counteracts the effects of a protein called HDAC1, which acts as a molecular brake on CLOCK and BMAL1 each night. From this, the scientists reason that rising levels of PER tell HDAC1 to put the brakes on its own production as the night goes on, which would eventually allow JARID1a to restart the cycle by kicking CLOCK and BMAL1 back into gear, which would start raising PER levels again. Now how’s that for an intricate clock?!

The researchers confirmed this idea by inserting the JARID1a gene into the fruit flies that lacked it – and sure enough, JARID1a released the HDAC1 brake and put the flies on a normal circadian cycle.

Scientists hope this discovery will aid the development of certain types of drugs – for instance, as people age, their circadian cycles seem to shorten, and the researchers suspect this may have something to do with JARID1a. People with certain types of diabetes also tend to have out-of-whack circadian rhythms, so similar drugs might benefit them as well.

As for nocturnal college students and rockstars, though, I suspect the solution may not be quite so simple.

Secret Sleep Memory

Our memories for certain types of info seem to improve more during sleep than during wakefulness, a new study reports.

A neuroscience researcher, hard at work on a complex problem.

Researchers have found that recall for pairs of words improves dramatically after a period of sleep, as does working memory capacity. An equivalent period of wakefulness results in much less improvement in these areas than sleep does, suggesting that a distinct type of memory consolidation may be happening during sleep.

Neuroscientists have known for years that sleep can help us learn. Watching or reading information right before you doze off can dramatically improve recall. Even physical skills, like playing an instrument or a sport, seem to improve more rapidly if a person practices right before bed.

What this new research seems to imply, though, is that “sleeping on a question” not only improves our understanding of that particular question, but on future questions of the same kind:

Memory for word pairs reliably improved after a period of sleep, whereas performance did not improve after an equal interval of wakefulness. More important, there was a significant, positive correlation between WMC [working memory capacity] and increase in memory performance after sleep but not after a period of wakefulness.

In other words, volunteers’ working memory, as well as recall for word pairs, improved substantially after a period of sleep – and this improvement was greater than after an equivalent period of wakefulness.

As the Journal of Experimental Psychology: General reports, a team led by University of Michigan’s Kimberly Fenn and Zach Hambrick selected 250 volunteers and tested them on their recall for pairs of words, as well as on their ability to hold multiple items in working memory at once. They then retested these same volunteers after a period of sleep, and after an equivalent period of wakefulness.

While not all the volunteers’ memories grew stronger after sleep, most showed at least some improvement, especially in working memory:

The correlation between WMC and performance during initial test was not significant, suggesting that the relationship is specific to change in memory due to sleep. This suggests a fundamental underlying ability that may distinguish individuals with high memory capacity.

In short, this may be evidence for a memory system distinct from the one that operates when we’re awake. These findings could eventually help lead to more accurate tests for intelligence – as well as more effective study methods tailored to an individual person’s memory style.

It also reminds me of a point I like to raise in discussions about consciousness, dreams, and so on: that the real question, I think, isn’t “What’s the point of sleep?” but “What’s the point of wakeful consciousness?” To put it another way, there’s a lot more going on “behind the scenes” than in the spotlight of consciousness – so exactly what evolutionary problem(s) does subjective consciousness provide a solution to? Seemingly obvious answers spring to mind, I’m sure – but still, this question never fails to provoke some interesting debate.

And on that note, I’m off to do some research for my next article – and then take a nap…for Science!

Sleepocalypse 2011

One of the images recorded by the fEITER system.

For the first time in history, scientists have recorded functional images of brain activity as humans shift from consciousness into unconsciousness.

What they’ve learned is that the process of falling asleep involves a variety of areas within the brain. Some of these areas systematically inhibit others, until an entirely different type of functional network is created:

The images show that changes in the anesthetized brain start in the midbrain, where certain receptors for a neurotransmitter called GABA are plentiful. From the midbrain, changes move outward to affect the whole brain; as [GABAergic] messages spread from region to region, consciousness dissolves.

GABA (short for gamma-aminobutyric acid) helps initiate inhibitory activity in the brain. Interestingly, it first seems to inhibit inhibition, leading to a state of slight excitation and euphoria. Over time, though, GABA also inhibits that excitatory activity, causing various areas of the brain to decrease their communications with other areas and “shut down.”

Here’s what anaesthesiologist Professor Brian Pollard from the Manchester Royal Infirmary says about seeing the images for the first time:

Our jaws ricocheted off the ground. I can’t tell you the words we used as it wouldn’t be polite over the phone.

I like to imagine he yelled things like “bollocks!” and “cor blimey!”

Anyway, the scans were taken with a new imaging technique known as Functional Electrical Impedance Tomography by Evoke Response (fEITER). It’s essentially the smarter descendant of electrical impedance tomography (EIT), which estimates electrical activity inside the body by measuring signals passing through electrodes attached to peoples’ heads. But fEITER goes one better by measuring detailed electrical activity deep within the brain.

By the way, the Greek word ἀποκάλυψις (apokálypsis), ancestor of the English word “apocalypse,” means “revelation” – or literally, a “lifting of the veil.” Hence the post’s title.


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