Neuroplasticity: What’s Sleep Got to Do with It?

We start with a powerhouse team of neuroscience researchers at the University of Wisconsin:  Giulio Tononi and Chiara Cirelli. These two have been wrestling to understand the basic function of mammalian sleep:  why do we do it? What critical functions does it serve?   In 2003, using a collection of EEG, fMRI and some behavioral memory data, they formulated a new theory on the role of sleep:  The Synaptic Homeostasis Theory, or SHY, for short [3].   This theory asserts four main points:

  • Waking life is characterized by a strengthening of synaptic connections (synaptic potentiation) and a growth of neurons and their component parts.
  • In order to prevent a runaway process of strengthening and growth, which would be taxing on energy supplies and the bony limits of our skull size, sleep selectively reverses these wake-based increases in structure and function through a downscaling, which removes the weaker, newer connections and preserves the more established and important ones.  The growth and revision actions are ultimately balanced resulting in a regulated and constant neuronal weight and size, a homeostasis of synapses., or SHY.
  • The downscaling of synaptic size and function is accomplished by a nightly component of our sleep assemblage, slow wave brain activity (SWA or slow wave sleep, SWS).  Tononi and Chiarelli review the electrochemical magic of how SWS accomplishes this downscaling in depth.
  • Last, they posit that this turnover process of neuronal growth and selective pruning allows for optimal human learning and memory.  It is the basis for taking in and remembering new information.

This theory has received a great deal of attention since its original publication in 2003.

It extends and magnifies the idea of neuroplasticity, suggesting that it occurs not only in adult mammals but that it occurs every night!  Day in and day out.  Again, nearly mind-blowing.

While Tononi and Cirelli marshalled lots of circumstantial evidence to support their original claim, their ideas remained untested until last year.  At that time, two research teams, using different and new technical methods, conducted a pair of studies that were able to evaluate this proposition in decisive fashion.

Published in Science, last year, De Vivo et al used electron microscopy to measure the size of a particular part of the synapse, the axon-spine interface, in over 7000 neurons from two different areas of mouse brain, that were obtained during sleep, on awakening, and after 8 hours of being awake [4].  The results were astonishing. Synaptic area was reduced by approximately 20% after each sleep period. Our brains selectively expand and contract on a nightly basis by 20%!   In further support of their theory, they found that the downscaling preferentially culled the weaker, newer synapses. That last point is relevant in the following way:  each day, we’re each exposed to thousands of new words, sounds, images, sensations, ideas, and interactions. If we remembered everything, our minds would become cluttered and inefficient. To improve the signal to noise ratio, we engage in ‘smart forgetting’ at night that allows us to dispense with the unimportant noisy inputs we all receive and hang on to only the most important new bits.  Though it used mice and not human brains, there is every reason to think that these cycles of daily growth and nightly reduction measured by this study captured a universal micro-architectural turnover process that occurs throughout the central nervous systems of all mammals.

The second examination of SHY was led by Graham Diering at John Hopkins, using another novel method [5].  Instead of counting and examining synapse size, this group measured the cellular signatures and molecular breadcrumbs left behind whenever neurons shift size, change their strength, or form new wiring attachments.  Just like any other building project, when the brain undertakes construction and rehab work on neuronal assemblies, it requires energy, materials and chemical support, the latter termed, trophic support. Trophic support comes in the form of special molecules like BDNF (Brain Derived Neurotrophic Factor) and NGF (Nerve Growth Factor) that encourage growth and neuronal sprouting.  Once construction is started, evidence of the renovation work can be found in several areas. One of the main ways, which brain cells enlarge, is through the incorporation of specialized glutamatergic receptors on their outer membranous layer. Another bulk-adding sign occurs when these receptors become activated through a chemical process of phosphorylation. Employing sophisticated protein fractionation techniques; the team isolated and measured the number of glutamate receptors, their activation level, and density in mice brains comparing the results between the waking and sleep states.  This molecular detective work produced complementary findings to the Di Vivo paper: the number and activation levels, thus the overall weight, of these major synaptic ingredients were reduced by approximately 20% after sleep compared to after wake. Together, these companion publications in one of the world’s most rigorous scientific journals, moves the synaptic homeostasis theory from proposition towards established fact. In so doing, it highlights, like nothing before, the reality and magnitude of neuroplasticity and its indispensability for emotional and cognitive health. Sleep downscales our brain on a nightly basis in the service of memory, and learning.

John Gottlieb, M.D.