Plasticity in gray and white: Neuroimaging changes in brain structure during learning

I'm just going to go ahead and say it. I love glia. I think they're going to rule the next decade of Neuroscience research. Long left behind as the neuron's "support cells", I think that by 2020 we'll see them come into their own.

Have you seen A Bug's Life? Glia are totally the ants (heroes) and the neurons are the spoiled grasshoppers.

(Harumph.  The paper I'm writing about here says glia out number neurons 6 to 1 which is what reminded me of this movie clip, but I just looked up this paper and they say the ratio is 1:1.  Ah well maybe the neuron isn't totally out of the running, but at least my favorite glial cell type - the oligodendrocyte - is winning the glia race, accounting for 75% of all glia in the neocortex.)

Anyway, why am I all gooey eyed over glia today?  Well, I just read this review paper by Robert Zatorre, R Douglas Fields and Heidi Johansen-Berg on plasticity during learning, and it specifically addresses the cellular mechanisms which could drive results observed by human neuroimaging studies.  In fact, the authors make a great point that we should continue to remember: while MRI may not be perfect at least we can image the whole brains of living, breathing, learning individuals.  We can even image the same individual multiple times as they learn.

The paper does an excellent job of explaining the differences between experience-dependent changes and preexisting factors.  With a cross sectional study you can't tell the difference between whether one group (for example, trained musicians) have different gray or white matter than another group (the musically "less gifted") because of their training or because the musicians had brains which were predisposed to learn to play an instrument.  Training studies, where you randomly assign participants to one group or another can demonstrate experience-dependent changes, and individual differences studies can be used to investigate how preexisting brain structures predict how successfully volunteers are learn a novel task.  Heritability studies in twin populations can disentangle, to some extent, the degree to which environmental and genetic factors explain variance in gray and white matter.

The authors then present the candidate cellular mechanisms which would underlie changes on MRI scans (see the beautiful figure below).  And what I got all excited about, was the fact that while neurogenesis (the growth of new neurons) is a possible candidate for structural change, the authors believe "neurogenesis is likely a minor factor in MRI changes" because the number of new neurons that are produced in the hippocampus in the adult brain is relatively small (and neurogenesis in other regions of mammalian neoxcortex is tough to pin down).

So make way for the gila!

Figure 3: (a) Cellular events in gray matter regions underlying changes detected by MRI during learning include axon sprouting, dendritic branching and synaptogenesis, neurogenesis, changes in glial number and morphology, and angiogenesis. (b) Changes in white matter regions include alterations in fiber organization, which could include axon branching, sprouting, packing density, axon diameter, fiber crossing and the number of axons; myelination of unmyelinated axons; changes in myelin thickness and morphology; changes in astrocyte morphology or number; and angiogenesis.

The other mechanisms for the changes observed on MRI scans included gliogeneis (the growth of astrocytes, oligodendrocytes and microglia), which has been demonstrated in the adult brain.  It's even been shown to be a response to learning and experience.  Synaptogenesis and axonal "pruning, sprouting or re-routing" are also listed as mechanisms for change.  So you may not have to create new cells, you may just reorganize the ones you already have.

This review paper describes signally pathways involving BDNF (brain-derived neurotrophic factor), VEGF (vascular endothelial growth factor), activity dependent release of ATP from axons, and L1-CAM (L1 cell adhesion molecule) and how they may affect change in macroscopic measures of gray and white matter.  I'm not going to repeat the paper here, but the sections are very well written and a great source of references.

Finally, the paper ends with the obvious and important point that considering changes in gray and white matter separately is highly artificial.  They're both made up of neurons and glia and their behaviors are tightly coupled.  The example of Nogo-A, a myelin protein which interacts with the Nogo-66 receptor on axons to inhibit their growth, which has also been found in neurons, is held up as a molecule which can control activity dependent interactions between glia and neurons in white and gray matter.

In conclusion: great review.  I may have started this blog post all about the glia (and I do still <3 them very much) but truly, the take home point is that changes we observe in MRI scans of living humans will be the interactions of neurons, glia and vasculature working together.

Plasticity in gray and white: neuroimaging changes in brain structure during learning.

Zatorre RJ, Fields RD, Johansen-Berg H.

Nat Neurosci. 2012 Mar 18;15(4):528-36. doi: 10.1038/nn.3045.

PMID: 22426254