New role for supporting brain cells

Glial cells, long thought to be supporting actors to neurons, play a crucial role of their own in regulating neuronal activity, according to a study published in Science this week. The study's results suggest that glial cells provide the link between neurons and the vasculature in the brain and central nervous system, and posit that the nervous system is controlled in a more complex manner than previously thought. "For a hundred years, we have known that glia existed," said linkurl:Mriganka Su

Written byAlla Katsnelson

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Glial cells, long thought to be supporting actors to neurons, play a crucial role of their own in regulating neuronal activity, according to a study published in Science this week. The study's results suggest that glial cells provide the link between neurons and the vasculature in the brain and central nervous system, and posit that the nervous system is controlled in a more complex manner than previously thought. "For a hundred years, we have known that glia existed," said linkurl:Mriganka Sur;https://www.mit.edu/~msur/ of the Massachusetts Institute of Technology, the study's main author. "We had very little idea what they do." At the turn of the 19th century, Spanish anatomist Santiago Ramon y Cajal used silver staining to identify neurons and glia as distinct cell types in the brain. The activity of neurons has been extensively studied electrophysiologically, but "because glia do not have action potentials, they were invisible to microelectrodes," said Sur. Researchers speculated that glial cells formed a continuous mesh that provided nourishment to neurons, or soaked up potassium left over from neuronal firing. During the past decade, however, researchers have begun to identify distinct receptors and transmitters in glia that hinted at a linkurl:more integral role.;https://www.the-scientist.com/article/display/22128/ "There was a hunch that they might have something to do with regulating blood supply to active brain regions in ways we do not understand," Sur said. Sur's group used an in vivo imaging method in which they labeled neurons and astrocytes -- the most abundant type of glial cell in the central nervous system -- with different colored dyes, and tracked calcium levels in the two cell types in response to linkurl:visual stimuli;https://www.the-scientist.com/article/display/15821/ in the cortex of ferrets. Mammalian visual cortical neurons have unique response patterns, where individual cells are tuned to distinct spatial orientations of a stimulus. "We showed that astrocytes have the exact same orientation and mapping as neurons have," Sur said. "That was a big surprise," suggesting astrocytes might be direct players in a job long thought to belong just to neurons. Brain imaging techniques such as linkurl:functional MRI;https://www.the-scientist.com/article/home/53137/ measure blood flow as a proxy of neuronal activity, but it's never been clear how the two factors are linked. This blood flow component is also evident in optical imaging, the technique Sur's group used. But when the researchers blocked astrocyte activity with a pharmacological compound, neurons remained active but the blood flow signal disappeared. "This shows at one glance that astrocytes are the intermediary between neurons and local blood flow," said Sur. In other words, glial cells play an active role in generating brain activity. Sur said his group is now using pharmacological blockers of astrocytes and studying knockout mice with altered astrocyte signaling to pin down exactly how astrocytes influence synapses. Recently, Christopher Moore, also of MIT, proposed that changes in blood flow actively regulate neuronal activity, an idea he calls the linkurl:Hemo-Neural Hypothesis.;https://web.mit.edu/MCGOVERN/html/News_and_Publications/2007_thinking_with_blood.shtml That theory and the study's results "fit very well together," said Sur. Neuronal activity might regulate blood flow via astrocytes, he suggested, and that change in blood flow would in turn modulate neuronal activity in a feedback loop. "It makes sense," said Sur, as "part of an integrated network in ways that go beyond presynaptic and postsynaptic signaling."