How brains work, how brain imaging works: Astrocytes

ResearchBlogging.orgBlood flow in the brain is linked to neuronal activity. Therefore, various 'brain scanning' techniques can be used to observe neuronal activity in the brain. This has led to an astonishing revolution in knowledge of how the brain works. Of course, you knew that already.

Also astonishing is that the reason for changes in blood flow in relation to what neurons are doing is unknown! We know this system works, but we don't know why!

Until now...

It turns out that it is the glia cells. There a different kinds of glia, and they are very important in brain function. Glia do a lot of different kinds of work in the brain. If the brain's neurons are the faculty, the glia are the department secretary, administrators, the janitorial staff, security ... everybody else. (We're not sure where graduate students fit into this ... perhaps further research will elucidate this mystery).

In particular, it turns out that a particular kind of glia ... Astrocytes ... bridge the gap between neuronal activity and blood flow. Astrocytes are actually involved in neuronal activity. They do not have very much electonic activity, and therefore, have gone largely unnoticed. You see, much early research on neurons involved observing their activitiy by sticking tiny electrones into nerual tissue. Astrocytes do not show up on that particular 'radar screen.' However, other observational techniques indicate that this particular kind of glial cell is involved in modulating neural activity.

According to one of the study's authors, James Schummers:

Electrically, astrocytes are pretty silent ... A lot of what we know about neurons is from sticking electrodes in them. We couldn't record from astrocytes, so we ignored them.

[When astrocytes were imaged with two-photon microscopy] the first thing we noticed was that the astrocytes were responding to visual stimuli. That took us completely by surprise ... We didn't expect them to do anything at all. Yet there they were, blinking just like neurons were blinking. We didn't know if the rest of the world would think we were crazy.

According to Mriganka Sur, another co-author:

This work shows that astrocytes--which make up 50 percent of the cells in the cortex but whose function was unknown--respond exquisitely to sensory drive, regulate local blood flow in the cortex and even influence neuronal responses. ... What's more, astrocytes are arranged in orderly feature maps, exquisitely mapped across the cortical surface in sync with neuronal maps.

So how did they figure this out? The researchers used a two-photon imaging of calcium signals in the visual cortex of a ferret (in vivo). Calcium would be active during cell activity because of its role in basic cell metabolism.

This kind of imaging involves looking at tissue with a fancy microscope that is able to focus on things happening at depth within that tissue. (By "depth" we mean about one millimeter.) The reason this works is rather spooky. Under certain conditions, two photons act in a quantum mechanical way to cause a fluorescent event which can be detected by the two-photon microscope.

Schummers, J., Yu, H., Sur, M. (2008). Tuned Responses of Astrocytes and Their Influence on Hemodynamic Signals in the Visual Cortex. Science, 320(5883), 1638-1643. DOI: 10.1126/science.1156120

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Awesome blog. Thanks!

The research linking astrocytes to control blood flow has been active and widely accepted for over a decade. (In fact that's the first sentence of their abstract). In fact, many molecular aspects of the mechanism linking neural activity to vasodilation using astrocytes is already known.

Astrocytes aren't the only thing that links neural activity to blood flow, but they are a key factor. This is not the unique aspect of your linked article.
The unique part is showing a unique way to image astrocyte activity to get spatial patterns of astrocytes and to use this method to demonstrate that glutamate transport is a major contributor to astrocytes and blood flow changes (something that has been shown using different methods before)

Correct me if I'm wrong, but technically fMRIs measure blood indirectly by measuring spikes in oxygen levels, a function of metabolism and not necessarily tans-neuronal electric activity. In talking with cognitive psychologists, one of the biggest hurdles to interpreting fMRI data is deciding what counts as background and what counts as signal. Interesting post though.

caynazzo. You're not quite right. fMRI signal changes are dominated my the levels of deoxyhemoglobin in the blood. This level is affected by two factors. First, the more metabolism (i.e. the more energy being used in a region) the more oxygen is used and the higher the deoxyhemoglobin levels. Second, the faster the blood flows to a region (more vasodilation) the higher the oxyhemoglobin levels and thus the lower the deoxyhemoglobin levels.

From the metabolism front, astrocytes have been shown to dominate much of the energy usage in the brain since they are heavily involved in the active transport of glutamate and other molecules across membranes. They also have direct involvement in causing vasodilation through Ca2+ levels and other factors.

As for the hurdles of fMRI, background vs. signal is a challenge, but, like all science, a well designed study can answer questions within the limits of the measurement method.

There's also an excellent (I think) article in Nature by Nikos Logothetis titled "What we can do and what we cannot do with fMRI."

It goes into detail on what higher and lower BOLD levels do and don't mean.

By Ryan Morehead (not verified) on 20 Jun 2008 #permalink

From the metabolism front, astrocytes have been shown to dominate much of the energy usage in the brain since they are heavily involved in the active transport of glutamate and other molecules across membranes. They also have direct involvement in causing vasodilation through Ca2+ levels and other factors.
Posted by: bsci

Very interesting. Can you recommend some papers on this stuff?



There's a lot of stuff on this.
Attwell & Laughlin 2001, J Cereb Blood Flow Metabolism 21(10) p1133 is a good general article on the energy budget of cells in the brain. (Note that it's not a completely solved model and you'll be able to find papers that reference this that disagree with their findings. One thing that makes these types of measures hard is that the ratios of different types of cells vary across species so the energy budgets might also vary.

Pellerin & Magistretti 1994 PNAS 91(22) talks about astrocytes and vasodilation
Chatton & Pellerin 2003 PNAS 100(21)

Attwell & Iadecola 2002 Trends Neurosci 25(12) talk about some Ca2+ effects
Other ionic controls of vasodilation are discussed in Lauritzen 2005 Nat Review Neurosci 6(1)
Buerk & Ances 2003 Neuroimage 18(1)

Other discussion of astrocytes are:
Zonta, Angulo 2003 Nat Neurosci 6(1)
Mulligan & MacVicar 2004 Nature 431(7005)

Peppiatt & Attwell 2004 Nature 431(7005) contrasts the models of the above two papers

Volterra & Meldolesi 2005 Nat Review Neurosci 6(8)
Patel, de Graff et al 2004 J Cereb Blood Flow Metab 24(9)
Parri & Crunelli 2003 Nat Neurosci 6(1)

I can write more, but since I was away for the weekend and don't know if you're still reading this thread, I figured I'd wait for a reply before putting in any more work.

Very much appreciated. Exactly what I was looking for.

Feel free to throw in a bunch more refs. No rush. I'll keep an eye on this thread for another couple of weeks (ahh, the wonders of bookmarking).

One thing I notice about those refs is that (with one exception) they are all relatively recent. Is that because you are deliberately picking recent ones to be more up to date, or because most work on this stuff has only been done relatively recently?

Thanks again.

A lot of this is recent. This all builds decades old literature on blood flow and metabolism, but the focus on exactly how neural activity changes blood flow wasn't as interesting a question compared to how neurons fire until the explosion of PET, fMRI, and optical imaging which all require a better understanding of this link. PET started its rapid growth in the early 80's and fMRI in the early 90's.

I can probably dig up some older ones, or you can using the references of the above references, but our knowledge has changed so rapidly in this area, that much of that stuff really isn't up-to-date anymore.

Interesting question is how can a lay person like myself (i.e. a baker of bread by training) increase the quality of neuron activity..increased uptakes of oxgyen..perhaps by application of cold lasers to increase photostimulation of red blood cells and thus increase oxgyen uptake...since you state that this particular kind of glial cell is involved in modulating neural activity. then can I use cold lasers somewhere in the 800nm range to increase neural activity,....such as in the long term application of treatment for Parkinsons disease?

I wish I had some science background..this is far more intersting than baking a few thousands pounds of bread or cookies..thanks..Troy in Texas..Sept. 2, 2010