Monthly Archives: August 2016

Why Do We Sleep? Keeping Those Pesky Excitable Neurons in Line

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“The subject of sleeplessness is once more under public discussion. The hurry and excitement of modern life is quite correctly held to be responsible for much of the insomnia of which we hear: and most of the articles and letters are full of good advice to live more quietly and of platitudes concerning the harmfulness of rush and worry. The pity of it is that so many people are unable to follow this good advice and are obliged to lead a life of anxiety and high tension. Hence the search for some sovereign panacea…” (British Medical Journal, SEPT. 29, 1894, Sleeplessness)

I am sure until you glanced at the date you could easily be forgiven for thinking this quotation was written only last week. The disturbance of “modern life” is far from a novel phenomenon that plagues the 21st century, and smartphones and technology cannot be solely to blame for the problems we see. As the quotation continues (you can read the full article here, page 719), it is clear that attempts to treat insomnia were not all that different from remedies people might turn to now.

Disturbed sleep is something we’ve all experienced at one point or another. That sleepless night before an important meeting, interview, or exam stress leaves us feeling groggy, less responsive, and annoyingly less prepared for the problem we have to face. It’s clear that even a night of poor sleep can cause a plethora of problems which make restoration theories of sleep enticing and convincing. However, it is still not certain how sleep might rectify the impaired functioning associated with a night of tossing and turning in bed.

One theory argues that sleep acts to quieten down brain activity which becomes increasingly noisy during the day. This ‘noise’ makes it harder to function in terms of laying down new memories, remaining vigilant, and maintaining a positive mood. There are plenty of studies which highlight problems in each of these areas following poor, or a complete absence of, sleep for even a single night.

Now, the brain is a noisy organ and is constantly busy keeping you alive and functioning. Even when you’re not ‘thinking’ anything, it is still possible to detect a network of activity associated with this resting state. However, when ‘noisy’ is used here, it is in reference to noise which may be more indiscriminate and impede normal brain functioning.

Synaptic Homeostasis Hypothesis

This theory is known as the synaptic homeostasis hypothesis and was put forward in 2003 by the psychiatrist, Dr. Giulio Tononi of the University of Wisconsin-Madison. This theory centres on the important role of slow wave sleep (SWS) during a night’s sleep. SWS is the predominant neural signal found during the third stage of NREM sleep, and is characterised by slow-synchronised oscillations across the cortex. It is associated with the deepest stage of sleep and with many restorative properties of sleep.

A paper by Christoph Nissen and colleagues, published just this week in Nature Communications, has shed more light on how sleep may help us function on a day to day basis, and has provided further support for the synaptic homeostasis hypothesis. Currently, most of the evidence for this theory comes from animal studies and indirect evidence from a handful of human studies. That is what made the recent study by Nissen particularly exciting.

Christoph Nissen and colleagues at the University of Freiburg explored how sleep, compared to sleep deprivation, was associated with changes in memory encoding, cortical excitability and neural mechanisms behind brain plasticity and learning. They examined a group of 20 healthy university students who all took part in the normal sleep and sleep deprivation portions of the experiment.

The team examined cortical excitability following a normal night’s sleep and sleep deprivation using transcranial magnetic stimulation (TMS) to induce a twitch in a participant’s hand. The TMS device allows scientists to deliver a pulse which can be used to inhibit or excite the neurons underneath its coil. A pulse to the appropriate location on the right side of the brain will produce a corresponding twitch to the muscle in the participant’s left hand. The strength of the pulse needed to produce a response, or twitch, can be used as a marker of how excitable that particular patch of neurons is. As a result, this technique provides a non-invasive and relatively simple way to test one of the synaptic homeostasis hypothesis’ predictions.

In addition, the group examined brain activity using electroencephalography (EEG) to further explore alterations produced by extended wakefulness.They also tested performance by examining participant’s memory through the use of a simple word pair test, and through their capacity for LTP-like plasticity using a paired stimulation method.  LTP, or long-term potentiation to give it its full name, has been argued to be the mechanism within the nervous system through which learning occurs. It is argued to play a large role in memory formation and so provides the researchers with another way to assess performance following extended wakefulness or sleep.

In their student sample, Nissen and colleagues found evidence of increased cortical excitability, poorer memory performance, and reduced LTP-like plasticity following a night of sleep deprivation compared to wakefulness. All of these support the synaptic homeostasis hypothesis and support the role of sleep in ‘resetting’ the neural activity to a baseline. It is argued that this is what allows us to continue on at our best after a night’s sleep and allows us to start efficiently storing memories of cute animal videos while at work.

Yet, the evidence for this is still in its infancy and it would be unwise to jump to conclusions about this research. Rather, it is another hat to throw into the ring of sleep science.

This work is still just a start, but it is an interesting and exciting foray into further understanding how sleep serves its important role in our lives. Furthermore, it also provides some interesting avenues for therapies which might try to capitalise on the ability of sleep to return neural activity to a set-point. There is already some evidence to support short-term sleep deprivation to help depression. A further understanding of sleep’s impact on the brain, or lack thereof, may help us manipulate this to our advantage.

Inquisitive Tortoise

References:

Kuhn, M. et al. Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex. Nat. Commun. 7:12455

Tononi, G., & Cirelli, C. (2003). Sleep and synaptic homeostasis: a hypothesis. Brain research bulletin, 62(2), 143-150.

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Why Do We Sleep? The Brain’s Waste Disposal System

Brain Pic

How does sleep help this fellow’s tubular brain remain healthy?

“Okay, smart guy so why do we sleep then? Bet you can’t answer that one…”

“Well… How long have you got? There’s a fair bit of content to co- Hey! Don’t run away! It won’t take me that long, honest!”

Sleep is complex and despite the intuitive explanation for why we drift off on a daily basis, we are still in our infancy when it comes to understanding how and why this occurs. We know that for the most part a good night’s sleep is refreshing and important for paying attention at work, school, or carrying out most tasks.However, how sleep keeps us functioning is less black and white.

There is no one reason why we need to sleep. For example, it maintains us mentally and physically in a number of ways, including:

  • Memory consolidation
  • Growth
  • Mental health
  • Brain maintenance

We could spend a lot of time covering all of these in considerable detail, but for now we’ll look at brain maintenance. Brain maintenance may seem like a broad category but it fits into our recent developments in understanding how the brain deals with waste materials.

The Brain’s Waste Disposal System

All cells in the body produce waste products of some description. This may be as a result of metabolic functioning, protein synthesis, and cell death, and these are filtered out via the lymphatic system.

The brain, unsurprisingly, is no different. However, until recently it was not clear how the brain solved this waste management problem. That was until the recent discovery of the glymphatic system.

Glymphatic System: The Brain’s Clearance System?

So what is the glymphatic system, and why should we care? Well firstly, its discovery has been hailed as important step in understanding major neuropathologies such as Alzheimer’s disease. Although, there’s a while to go before we should get too excited about this.

As mentioned above, the cells within your body work and produce potentially toxic waste products. The body has an effective way of getting rid of these through multitudinous lymphatic vessels. Yet, until recently it wasn’t known how the central nervous system, that is the spinal cord and the brain, manage to remove their waste products.

In a similar way to the lymphatic system, it has been proposed than the glymphatic system works by removing waste products from the central nervous system (e.g. spinal cord and brain). This is achieved, in part, by the exchange of solutes or waste products between cerebrospinal fluid (CSF) and interstitial fluid (ISF).

The system is comprised of a series of channels which appears to “piggyback” off blood vessels within the brain. It is argued that the movement of arteries, as a result of blood-flow, helps to move the cerebrospinal fluid through the brain (CSF). This enables the movements of waste between interstitial fluid (ISF) which bathes cells and CSF which runs alongside blood vessels in the brain. However, the glymphatic system also includes the presence of specific glial cells, known as astrocytes, alongside these channels. The function of the astrocytes is to facilitate the movement of particles between CSF and ISF. Without their presence, the movement of waste would be too sluggish to respond appropriately to the changing demands of the hungry organ we call the brain. It is the presence of glial cells, and the similarities to the lymphatic system, which give this glymphatic system its name.

Waste Disposal While You Sleep

How does all of this relate to sleep? Well, a recent collection of studies has provided some evidence that sleep may facilitate the movement of toxins from the brain via the increased activity of the glymphatic system.

One particular toxin produced as a waste product of brain cell activity is called amyloid beta. This toxin is linked to severe progressive diseases such as Alzheimer’s, and there is considerable research trying to work out how to mitigate its destructive effects. Last year, a group of scientists lead by Professor Maiken Nedergaard at the University of Rochester Medical Centre found that the brain’s drainage of amyloid beta was increased during sleep and anaesthesia-induced unconsciousness compared to during wakefulness in mice. More specifically, it seems that the capacity of the brain to flush out such harmful toxins is enhanced due to the area between cells, interstitial space, expanding by as much as 60 per cent. This seemingly enables a greater opportunity for such toxins to be removed via the glymphatic system.

In addition, the same group also found earlier this year that this process of washing harmful toxins out of the brain during sleep is enhanced based on the position of the mice studied. It was found that the removal of amyloid beta was enhanced when the mice slept on their side rather than their back. Interestingly, in both cases, it seems that anaesthetised mice showed the same effects as sleeping mice for the removal of amyloid beta and benefit of sleep posture.

This suggests that sleep may help with the maintenance of our brains by enhancing the waste disposal system we have in place. It may also provide some evidence as to why dementia and serious psychiatric illnesses are associated with sleep disturbances prior to the emergence of symptoms. However, this is all speculative and uncertain at this point. For a start, these studies have only been conducted on mice, and due to the nature of the experiment it is not likely that they would be conducted on humans any time soon. That’s not to say that the same mechanism might not be occurring within humans, but it is rash to jump the gun and assume it is.

Regardless, it will be exciting to see how research in this area advances and what it can teach us about the importance of sleep.

Inquisitive Tortoise

References:

Lee, H., Xie, L., Yu, M., Kang, H., Feng, T., Deane, R., … & Benveniste, H. (2015). The effect of body posture on brain glymphatic transport. The Journal of Neuroscience, 35(31), 11034-11044.

Xie, L., Kang, H., Xu, Q., Chen, M. J., Liao, Y., Thiyagarajan, M., … & Takano, T. (2013). Sleep drives metabolite clearance from the adult brain.science, 342(6156), 373-377.

Further Reading:

https://www.urmc.rochester.edu/labs/Nedergaard-Lab/projects/glymphatic_system (From the horse’s mouth; a better description of what I’ve tried to convey in this post!)

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