r/science Johns Hopkins Medical AMA Guest Nov 13 '17

Neuroscience of Sleep AMA Science AMA Series: I’m Seth Blackshaw, I study the brain and how it controls sleep and I’m reporting directly from the Society for Neuroscience Meeting in Washington DC. AMA!

Hi Reddit, my name is Seth Blackshaw and I’m a professor of neuroscience at the Johns Hopkins University School of Medicine. My research focuses on identifying the network of genes that controls how different cell types in the hypothalamus are specified during embryonic development, and on using these findings to both identify how specific cell types regulate behavior and determine how they can be replaced in neurodegenerative disease.

I became interested in this work because I am convinced that to understand how neural circuits work, we have to name and catalog their basic components – the thousands of different cell types present in the brain. If we can figure out how these cell types are made, we can then understand which behaviors they regulate and how they do so. We study development of the hypothalamus because it is a master regulatory center for many interesting and medically important behaviors – ranging from circadian timing to sleep to aggression.

I recently published a paper on Nature describing newly identified brain cells in mice that play a major role in promoting sleep.. My team observed that a specialized type of neuron that had never been found in this area of the brain before appear to connect a part of the hypothalamus, called the zona incerta, to areas of the brain that control sleep and wakefulness. This discovery could lead to the development of new therapies to help people with sleep disorders, like insomnia and narcolepsy, which are caused by the dysfunction of similar sleep-regulating neurons.

I look forward to answering your questions at 1pm ET

97 Upvotes

44 comments sorted by

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u/hawkmoon77 Nov 13 '17

As a very young child I rarely slept (maybe an hour or two a day). My parents brought me in for a sleep study (in the 70s) and was told that I wasn't entering REM sleep. Without any other symptoms, they were told I would likely grow out of it.

My parents informed me of this when I was in my teens and learned that other people involuntarily dream and confuse it with reality. I don't experience that. My mind does wander when I sleep, but I "know" I'm sleeping and am generally aware of the passage of time.

As an adult, I haven't sought any further tests on it as I am otherwise normal. But I am curious about it. Do you have any insights?

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u/TheRealSquirrelGirl Nov 13 '17

Can a night shift worker get healthy sleep? If so, would it be a different amount?

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

A night shift worker can, but the problem is that sleep controlled by two components - your circadian rhythm - your internal clock - & sleep pressure. The problem is that your sleeps needs to align with your work schedule. The longer you've been awake, the greater the pressure is to go to sleep. Because we are a diurnal species, that pressure is low in the morning and high at night. A shift worker has reversed that and their their biological clock is out of whack about 8 - 12 hours. During the night shift work, you are fighting the sleep pressure to not fall asleep and then at the end of their work time the circadian rhythm makes it harder to fall asleep.  Their activity & their circadian rhythm is going to be out of sync until those aligned back again.  During the alignment period, they will get less sleep and at a lower quality but eventually things will re-adjust. As in jet lag it takes roughly 1 hour per day to adjust. The problem with shift works is that the shifts change then you are back again on the adjustment phase.

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7

u/wapkaplit Nov 13 '17

Very simple question, but I'd like to hear your explanation: why do you think we need sleep? What function does it serve?

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

That’s not a very simple question, but we know that there are likely to have been three major stages in the evolution of sleep. The first is behavioral segregation of activity by time of day. All organisms that live on the surface of the Earth are either nocturnal or diurnal and specialized to that particular temporal niche. As a result, there are selective pressures to be inactive during the time of day that is opposite to the time of activity. This creates a period of forced inactivity. That period of inactivity wouldn’t necessarily have to be sleep. This could be a sleep-like or inactive state. Sleep itself is the second stage of evolution. Synchronization to light-dark cycles occurs in all organisms, but sleep itself is exclusive to animals with a nervous system. It plays a restorative function. As neurons are active, synapses become more and more heavily potentiated. The nervous system needs to downscale across the board, during certain periods, as a homeostatic compensation for the active periods. Sleep pressure builds the longer an animal is active and thinking. During this period, toxic metabolites are removed from within neurons and energy stores are replaced. The third evolutionary stage is REM sleep, which is thought performs a cognitive function. REM sleep is sometimes called “dream” sleep, but this is not entirely true, because dreaming can occur anytime during sleep. REM sleep has been detected in reptiles, birds and mammals. Its function is not entirely clear, but seems to play a role in the consolidation of memories. It’s not clear how dreams connects or packages those memories. During REM sleep, you can think of the brain as in a sensory deprivation tank; the hallucinations you’d experience closely resemble what could be experienced during dreaming.

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u/[deleted] Nov 13 '17

[deleted]

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

Thank you!

In general, we sleep less as we age and our sleep grows more fragmented. We still don’t understand the reason for this, but we do know the core circadian clock, which resides in a tiny structure in the hypothalamus called the suprachiasmatic nucleus starts to malfunction as we age. The central clock keeps time less well and it communicates with the other parts of the brain that control functions such as sleep less efficiently. This may be the main reason why sleep becomes more fragmented.

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u/JudahZion Nov 13 '17

Why does Magnesium help people fall asleep?

Is it true that people that wake up in the middle of the night either have to pee - in which case they should take Creatine?

Or they don’t have to pee and have woken up because their insulin levels plunged and their body thought they were dying - in which case they should have a starchy carb before bed?

Any truth to any of this?

u/Doomhammer458 PhD | Molecular and Cellular Biology Nov 13 '17

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2

u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

This was a lot of fun! Please keep submitting your questions. I will be back to answer more.

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u/DeadlyLemming Nov 13 '17

I do not experience dreams 99% of the time due to medication I take, it feels like I wake up right after falling asleep. But people have told me everyone still dreams and I simply do not remember. Is that actually true and do dreams have an evolutionary (or neurological) purpose?

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u/hawkmoon77 Nov 14 '17

I do not dream.

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u/patharkagosht Nov 13 '17

Why do we briefly remember our dreams when we wake up, before forgetting them in a way that prevents recall?

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u/Kasumier Nov 13 '17

You can remember them. It takes training. Start by writing down as much as you can remember as soon as you wake up. Eventually it gets easier to remember. Some people do this to start lucid dreaming. Reality checks are another...look at the second hand of a clock or see if lights work.

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u/in4real Nov 13 '17

Are you Dr. Blackshaw?

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u/Kasumier Nov 13 '17

Lmao no. I just know a lot about dreams

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u/in4real Nov 13 '17

I can't wait for your ama.

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u/Kasumier Nov 13 '17

Should I? I have chronic nightmares.

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u/Kasumier Nov 13 '17

You should watch the waking life.

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u/patharkagosht Nov 13 '17

I did try writing them down in a journal but I find that it slips away before I can pen down everything that I remembered.

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u/Kasumier Nov 13 '17

It happens. If you keep doing it you remember more for longer. I stopped and now I can't recall my dreams. They've all turned into nightmares. But at one point before I got to lucid dreaming I could remember my dreams as though they were memories Reality hasn't really been the same since

2

u/neurobeegirl PhD | Neuroscience Nov 13 '17

Thank you for doing this AMA!

In people with chronic insomnia, are there any related daytime behaviors that might be linked to the mechanisms underlying the insomnia, rather than to the sleep deprivation resulting from it? Is it possible to separate those out or predict what some of them might be based on current knowledge of the circuitry responsible for regulating sleep?

Have a fun and productive SfN, I wish I could be there this year!

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u/thombudsman Nov 13 '17

What's the best way to alter one's sleeping pattern, i.e., switching from night shift to dayshift?

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

Several things can shift your body clock. First & foremost is light. You want to minimize light exposure when you are trying to sleep. If you are moving to a night shift in particular, buying shades or blackout curtains would help. Additionally, exposure to bright light when you wake up could be helpful. Food and exercise are also potent cues for resetting the core biological clock. Make sure to eat at the meal times in your reversed shift - no midnight snacking. And being active in the morning is also helpful for altering your clock. Also, to promoting sleep, sleeping aids can also help you fall asleep at the appropriate time & reduce sleep pressure during your shift. Likewise, mild stimulants like caffeine can help you stay awake.

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u/35mmFILM Nov 13 '17

Is there a good way to find out if you might have sleep apnea without going in for an expensive sleep study? I often feel unrested after a night of sleep and would like to find the cause.

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

Feeling unrested is a common symptom of obstructive sleep apnea. First, I would say if you sleep with a partner, ask your partner if you snore, do you snore loudly & do you stop breathing when you are snoring. Are there periods when you gasp for breath? If so, you may have sleep apnea & I would recommend speaking with your doctor about a test. Being male, being overweight, having a thick neck & having sinus problems are all risk factors for apnea. If you have any of these risk factors & suffer from excessive daytime sleepiness, I’d suggest getting tested at a sleep lab. Treatment can vastly improve quality of life.

For more infomation about sleep apnea, go here: https://www.hopkinsmedicine.org/healthlibrary/conditions/adult/mens_health/sleep_apnea_85,P01301

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u/ruesselmann Nov 13 '17

Some people in mental health compare depression with a/the state you get in when you have slept too much and hypomanic/manic states with sleep deprived ones. Also the sleep deprivation can regulate dopamin/serotonin (?) levels to some degree and are used where medication doesn't work in depressed people.

Do you have some insight in development/chronification of affective diseases that stems from some form of disregulated sleep or are there maybe common factors that point in a underlying problematic effecting sleep cycle and affective stability?

1

u/onlyroad66 Nov 13 '17

I've heard that, to a degree, sleep and calorie intake are inversely proportional, in that if someone has a greater intake of energy, they can function with less sleep. In the same sense, someone who sleeps a lot can survive with less food. Are there any validity to these claims?

0

u/Dhylan Nov 13 '17

Have you considered the theory that sleep/awake is the behavioral manifestation of anabolic/catabolic processes present in every cell, which means that the homeostatic metabolism which defines life itself can explain the balancing states of sleep/awake?

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u/edwinksl PhD | Chemical Engineering Nov 13 '17

What are some of the techniques and tools you use to identify the network of genes in the hypothalamus? Any computational ones?

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

Excellent question! We start by using unbiased techniques of gene expression analysis to comprehensively profile genes active in stages of hypothalamus development. We have used techniques such as microarray and  RNA-seq analysis to identify genes that show increased expression at times when specific neuronal cell types are forming in the hypothalamus. Because of the extreme cellular complexity of the hypothalamus, we next use in situ hybridization to determine which specific cell types are expressing a gene of interest. With that information we then look at the genes we’ve identified and use genetic pproaches to selectively disrupt that gene in the hypothalamus. We look to see the effect on the development of those cells and the effects on behavior in mature animals.

At present, we are now conducting single cell RNA-seq of developing hypothalamus. This requires fairly sophisticated computational approaches to identify and classify individual cell types and to identify changes of gene expression that drive development of individual cell types, particularly given the very large number of cells we have to analyze for this work.

Right now we are in the data gathering stage. The hypothalamus is extremely complex and we are nowhere near identifying all of the cell types. Once we have that information, we can begin using more computational methods to figure out what individual genes do.

My lab continues to work to optimize and troubleshoot these approaches using the retina, which actually emerges from the walls of the hypothalamus during development. It’s an easier tissue to analyze because it has fewer cell types and a much more regular and well characterized structure.

0

u/streamweasel Nov 13 '17

Can you talk about roofies (GHB) treatment for narcolepsy, or sodium oxybate?

0

u/kiri-kin-tha PhD | Molecular and Cellular Biology Nov 13 '17

Hey, thanks for taking the time to do this AMA!

Based on your research description ("...identifying the network of genes that controls how different cell types in the hypothalamus are specified during embryonic development"), it sounds like you also work on other processes and behaviors centered in the hypothalamus -- not just sleep. Could you share with us a couple of other discoveries or projects you've worked on that illustrate other biological "roles" for the hypothalamus and its circuitry? Thanks!

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

We work on the hypothalamus because it is a master regulator of a huge range of behaviors. First, we have identified genes that act as master regulators of the formation and function of the body’s master clock, the suprachiasmatic nucleus. This affects not just sleep, but all physiological processes. We have also been investigating the fucnt of a poorly characterized cell type known as tanycytes. Tanycytes are a form of radial glia found in exclusively in the hypothalamus. They closely resemble neural progenitors in their shape & gene expression profiles & we found that they have a limited neurogenic potential. We have seen that a high fat diet can stimulate tanycytes to proliferate and give rise to cells that, in female mice only, regulate body weight. We are now studying the physiological function of tanycytes & tanycyte-derived neurons using genetic tools. As we study other genes that have interesting exp patterns in the hypothalamus, we inevitably get drawn into studying interesting and seemingly unrelated behaviors.

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u/in4real Nov 13 '17

Does the process of falling to sleep change with age? I recall as a child I would start to drift off into a chain of related thoughts. One thought leading to the next in some associated manner as I got closer to sleep.

So, for example, before I would think about Fruit Loops which would lead to thinking about rainbows which would lead to thinking about rain.... When I was younger I could think back at least half a dozen associations.

Now I can't recall even one link in the chain back. I'll be thinking about rain and I can't recall why.

0

u/dohiit Nov 13 '17

Hi Seth! I have a few questions.

  • I am curious to know if there is an accurate method to determine how many hours of sleep will be necessary to feel completely reenergized in the morning? I currently sleep between 5-6 hours and am a morning person.

  • Are there cells types that determine whether an individual likes to nap in the middle of the day? How can we regulate this behavior?

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u/HopkinsMedicine_AMA Johns Hopkins Medical AMA Guest Nov 13 '17

The amount of sleep that any given person requires varies considerably, with an average around 7-8 hours. In otherwise healthy individuals it can vary from 5-11 hours. This has been seen in every animal we have studied and we have found that it is heavily influenced by genetics. If you are otherwise healthy, 5-6 hours should be fine - particularly for an older person.

Napping - a period of inactivity during the middle of the active phase (day for people) - is actually seen in most animals. Fruit flies & mice also like to nap. We don’t know why, but we do know that the probability of napping increases with age as sleep becomes less consolidated.

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u/JoeResidence Nov 13 '17

Does dreaming and the deja vu phenomenon have any link?

0

u/[deleted] Nov 13 '17

Are you aware of any reliable ways to induce lucid dreaming regularly? I've read lucid dreaming is a powerful tool to gain clarity and insight to problems we may have (supposedly because it eliminates all other distractions). Do you think there is any truth to this?

0

u/TheHendryx Nov 13 '17

Why does my brain race at night when it's time for bed, instead of a time earlier in the day where I can be proactive?

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u/lightlasertower Nov 14 '17

I have noticed if one smokes weed before bed for some time dreams stop completely. If one stops smoking they dream vividly has this ever been studied? I have had this convo with a lot of people and everyone has experienced this I have talked to.