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October 22, 2011

Sleep and spines modulate your mind...and your brain?

"The mind is the brain doing its job." - Simon LeVay, 1994

We know that sleep is good for us: it's a daily, regularly- or irregularly-scheduled body and brain maintenance check. The sleep/wake cycle maintenance staff in particular is profoundly important in synaptic renormalization (homeostasis) by modulating (decreasing) synaptic size and/or strength in the adult brain. In the adult brain; surprisingly, this doesn't exactly hold for the adolescent brain, where sleep/wake cycle maintenance staff is responsible for more synaptogenesis (synaptic formation) and synaptic pruning (synaptic elimination).

A recent article published in Nature Neuroscience examined the process of cortical development (that involves synaptogenesis and pruning) in adolescent YFP-mice (through two-photon microscopy) as a function of different sleep/wake cycles: W1S2 mice (wake followed by sleep), and S1W2 mice (sleep first followed by wake). Mice were allowed to sleep or kept awake for each behavioral state (sleep/wake) for durations that mimic physiological sleep/wake cycles (6-8 h) and then imaged. Interestingly enough, they found overall decreased spine density in W1S2 mice and increased spine density in S1W2 mice; there was no variation observed in mice in early or late adolescence. Waking results in a net increase in cortical spines, and sleep is associated with net spine loss.
A third experimental group of W1SD2 mice (wake followed by sleep deprivation), to control for decreased spine density as a function of the passage of time showed a net increase in synaptic density.

In summary:
Wake followed by sleep (W1S2) = spine loss
Sleep followed by wake (S1W2) = spine gain
Wake followed by sleep deprivation (W1SD2) = spine gain

Sleep might actually be bad! (...for dendritic spines, that is)

The wake-sleep deprived group presents an interesting case. Sleep-deprivation, akin to pulling an all-nighter, shows a net increase in spine density. Therefore, sleep deprivation is one way to keep your dendritic spine density (that is, until you crash of exhaustion). Sleeping for the recommended 8 hours a night is also a default option. For those of us in adolescence, retaining spine density though sleep-deprivation is still theoretically a viable option. A different experiment conducted by the same researchers imaged the mice after 2-3 hours of sleep (short sleep) or wake (short wake). Both groups showed no net changes after short sleep or short waking. It may be theoretically possible to maintain spine density through a sleep-deprivation following wake with short sleep sleep/wake cycle (power naps anyone?).

This article concludes by suggesting that behavioral state modulates spine turnover in a manner consistent with the need for synaptic homeostasis; in the adult brain this translates into synaptic renormalization, and in the adolescent brain (regardless of exact developmental stage of adolescence) this translates into synaptogenesis and synaptic pruning. Sleep may therefore facilitate spine elimination or spine loss in certain phases of development. Sleep deprivation during adolescence may affect synaptic turnover, as it blocks sleep-related spine pruning; however, it does not result in a further increase in spine density. It is currently unclear to what extent the role of sleep in spine elimination is permissive and/or instructive.

So what does sleep and spine density have to do with anything? In the adult brain, it decreases synaptic size and/or strength; in the adolescent brain, it modulates synaptic pruning during a period of massive synaptic remodeling. Synaptic spine density is a part of how the brain does its job. Spine density therefore affects the mind (the brain doing its job that feeds to the mind). Changes in our minds are therefore a result of the brain doing its job differently, and how the brain does its job differently can involve changes in synaptic spine density. Spine density subsequently affects the different jobs of the brain; spine density affects the mind. Sleep (the sleep/wake cycle), therefore, is especially critical in cortical development during adolescence in modulating synaptic spine density (long-term potentiation anyone?)

I should probably get more sleep myself...

Posted by      Patricia W. at 10:19 PM MDT


  Christina U.  says:
I am slightly confused. Do these data only apply to adolescent brains and the formation and pruning of the dendrites during that time in your life? Secondly, regarding the sleep deprivation study, do you know how long, from the beginning of the experiment to the end, the mice were sleep deprived (in hours)? That part made me wonder about the negative side effects that can arise from prolonged sleep deprivation followed by power naps, or the like.
Posted on Mon, 24 Oct 2011 6:01 PM MDT by Christina U.
  Patricia W.  says:
This particular study focused on the adolescent brain so yes to your first question. In the adult brain the synapse strength is the only thing that changes (the paper mentions size). In terms of the sleep deprivation, what they explicitly give is 6-7 hours of sleep deprivation during the day; also included though is sleep deprivation after waking at night, where they don't specify the exact time. For the last question, though they don't address this, I think studying that in a mouse and then translating that to a human would be challenging, but maybe someday these researchers might decide to look into it!
Posted on Thu, 27 Oct 2011 7:49 PM MDT by Patricia W.
  Christina U.  says:

Thanks for responding to my question in such depth. I, too, hope that there will be more studies that actually link our sleep needs to those of the mice as well, it would be interesting to finally learn how we can improve our sleep habits to maximize our cognitive abilities.
Posted on Thu, 27 Oct 2011 8:55 PM MDT by Christina U.
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