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What is Sleep?/GinaPoe

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Notes by user Gina Poe (UCLA) for What is Sleep?

Post-meeting Reflection

1+ paragraphs on any combination of the following:

  • Presentation highlights
  • Open questions that came up
  • How your perspective changed
  • Impact on your own work
  • e.g. the discussion on [A] that we are having reminds me of [B] conference/[C] initiative/[D] funding call-for-proposal/[E] research group

I like starting our meeting “What is sleep?” with a session on function, because sleep looks different in different animals. so to figure out what sleep is we need to figure out what it does, then figure out what is necessary (conditions) to do that function then look for those conditions across ages and species.

Of course we have to start with some fundamentals and commonalities of sleep, even though we don’t know if they do - or should - define sleep or whether it is incidental-- a side effect, instead of an essential to sleep. I believe that thanks in part to the people here today, we have that starting point. We also have some basic functions of sleep identified, although it has been messy because until recently we have not known enough about those functions to adequately test whether sleep is important to those functions. But, again, we are at the point where we we have enough clues to start our reverse engineering phase.

In those early days we could not reverse engineer because we haven’t known what brain areas were responsible for what kind of learning and what neurotransmitters and electrical activity signatures were needed. But now, thanks to a horde of thousands, we know a few essential things:

Theta, gamma,

ACh, NE/DA

Phosphorylation

Potentiation/depotentiation, engrams, ARC, cFos, mRNA, protein synthesis,

Circuits: what is interconnected. How specifically NE and ACh targets forebrain,

Order of play: cortical registration, Hippocampcampal assembly, and eventual cortical strengthening...

Now we are ready to roll up our sleeves and figure out what sleep really is!

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Why awakening-based sleep deprivation is not great:

  1. As Jerry Seigel points out, if you wait until an animal shows electrographic or behavioral sleep beforee you awaken it, then you get the arousal-response.
  2. My 2016 Sleep paper shows (replicated by Duran et al., 2017) that cortical electrographic signs of sleep misses much subcortical sleep even normally... how much more when sleep pressure is high! We also show that hippocampus is in REM when when the neocortex remains in NREM normally, but even more when the hippocampal homeostatic drive (learning-induced) is high. Thus, any sleep deprivation protocol that relies on posture, EEG, or muscle tone would and probably does miss a lot of sleep that goes on "locally". Thus any negative finding, e.g., "REM sleep is not important for X learning task" could be completely wrong if we are not measuring that particular type of sleep from the area involved in that type of learning and/or memory consolidation. Recommendation: measure the amount of sleep from the actual structure essential for the function you are testing.
  3. Some of the sleep deprivation studies use pharmaceuticals like caffeine or some other stimulant, which is good because it eliminates the awakening response discussed in point 1 above, but of course stimulants have their own effect on the function under study.

-------On time variances of total sleep time vs sleep bout lengths----------

One function of sleep, like the memory process of sleep, may take only a few minutes or even seconds to accomplish, while other functions of sleep, like repair and clearance, may take much longer to accomplish, and be counterproductive to the learning function, and therefore sleep may need to intersperse the learning function at intervals during the longer sleep period in order not to lose, e.g., what you consolidated.

Either the undoing of one sleep state's function by another or the processes or side effect outcomes of one state requiring another sleep state to clean up after it may be why healthy sleep proceeds in an orderly fashion and unhealthy sleep, even if it is adequate in total length is disordered: REM sleep occurring too soon in depression, REM sleep occurring at sleep onset in narcolepsy, etc. If REM sleep serves to clean up synapses (strengthens those spuriously weakened but tagged for keeping, and weakens synapses spuriously strengthened by SWS or those ready to be erased now that slow-oscillation coupled spindles have consolidated them to their final place) then that would explain why the length of REM sleep is related more to the length of the prior NREM state than to the length of waking.

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It may be that the cycles of sleep are timed as they and the states follow each other in order as they do because should our planned long sleep cycle be interrupted, we will at least get some of all of the different kinds of necessary work done. even though having only one cycle leaves it incomplete, it would be better than nothing. Interrupting a sleep cycle midway (e.g. being awakened out of SWS) may be like interrupting the wash cycle midway, leaving clothes soaked and soapy rather than rinsed and clean. A power nap with only stage 2 sleep may be like a quick rinse and spin-dry which is better than the dry but filthy state that the party of wakefulness has left us. But a sleep disturbed from slow waves may, like the middle of the wash phase with soap and soaking wet, leave our brains in a worse state than the previous dry filthy one.

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Reference material notes

Some examples:

  • Here is [A] database on [B] that I pull data from to do [C] analysis that might be of interest to this group (insert link).
  • Here is a free tool for calculating [ABC] (insert link)
  • This painting/sculpture/forms of artwork is emblematic to our discussion on [X]!
  • Schwartz et al. 2017 offers a review on [ABC] migration as relate to climatic factors (add the reference as well).

Here is an excellent paper clearly spelling out all the hypotheses related to sleep for learning and forgetting (besides Susan and my J Neurosci 2019 articles!) - Jesse J. Langille, Remembering to forget: A dual role for sleep oscillations in memory consolidation and forgetting. Frontiers in Cellular Neuroscience 13:1, 2019. dob: 10.3389/fncel.2019.00071

Reference Materials

Title Author name Source name Year Citation count From Scopus. Refreshed every 5 days. Page views Related file
REM sleep selectively prunes and maintains new synapses in development and learning Wei Li, Lei Ma, Guang Yang, Wen Biao Gan Nature Neuroscience 2017 0 0
Experience-dependent phase-reversal of hippocampal neuron firing during REM sleep Gina R. Poe, Douglas A. Nitz, Bruce L. McNaughton, Carol A. Barnes Brain Research 2000 0 0
Antidepressant suppression of non-REM sleep spindles and REM sleep impairs hippocampus-dependent learning while augmenting striatum-dependent learning Alain Watts, Howard J. Gritton, Jamie Sweigart, Gina R. Poe Journal of Neuroscience 2012 0 0
Input source and strength influences overall firing phase of model hippocampal CA1 pyramidal cells during theta: Relevance to REM sleep reactivation and memory consolidation Victoria Booth, Gina R. Poe Hippocampus 2006 0 0
Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory Kevin M. Swift, Brooks A. Gross, Michelle A. Frazer, David S. Bauer, Kyle J.D. Clark, Elena M. Vazey, Gary Aston-Jones, Yong Li, Anthony E. Pickering, Susan J. Sara, Gina R. Poe Current Biology 2018 0 0
Remembering to forget: A dual role for sleep oscillations in memory consolidation and forgetting Jesse J. Langille Frontiers in Cellular Neuroscience 2019 0 0
REM restriction persistently alters strategy used to solve a spatial task Theresa E. Bjorness, Brett T. Riley, Michael K. Tysor, Gina R. Poe Learning and Memory 2005 0 0
Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex Guang Yang, Wen Biao Gan Developmental Neurobiology 2012 0 0
Sleep is for forgetting Gina R. Poe Journal of Neuroscience 2017 0 0
The human emotional brain without sleep - a prefrontal amygdala disconnect Seung Schik Yoo, Ninad Gujar, Peter Hu, Ferenc A. Jolesz, Matthew P. Walker Current Biology 2007 0 0
Homer1a drives homeostatic scaling-down of excitatory synapses during sleep Graham H. Diering, Raja S. Nirujogi, Richard H. Roth, Paul F. Worley, Akhilesh Pandey, Richard L. Huganir Science 2017 0 0
The function of dream sleep Francis Crick, Graeme Mitchison Nature 1983 0 0
Cognitive neuroscience of sleep Gina R. Poe, Christine M. Walsh, Theresa E. Bjorness Progress in Brain Research 2010 0 0

Presenter on the following Agenda items

Is sleep for remembering or forgetting?

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