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Solving the Mystery of fMRI

Researchers determine which cells mediate the blood flow tracked in fMRI.

When the cells of the brain were first described more than a century ago, they were grouped into two major categories: neurons and glia, Greek for “glue.” As the name suggests, the glia is often seen as little more than cellular spackle and caulk holding together the fine architecture of the neurons, which do the important work of transmitting and storing information. But a new study in Science from researchers at MIT reveals that glia cells might have a far more complex and active role in the brain–and even in diseases affecting it.

Brain at work: Microscopy images show a field of neurons (green) and astrocytes (purple) in the visual cortex of living animals. Astrocytes appear to respond to visual stimuli as neurons do.

The researchers describe experiments showing that a type of glia cells called astrocytes respond to visual stimuli along with their neighboring neurons in the visual cortex. Furthermore, the study shows that astrocytes are responsible for sparking the movement of blood into an area of brain activity, the same influx that provides a signal for brain-function studies using MRI.

The findings solve a long-standing mystery as to what functional MRI (fMRI) studies are actually detecting. And because of the importance of blood flow to brain function, the findings also raise the possibility that astrocytes have a previously unrecognized role in brain disorders.

Earlier research on cells taken out of the body suggested that astrocytes might be capable of feats previously attributed only to neurons. But in the new study, the researchers, led by Mriganka Sur, a a professor of neuroscience at MIT, looked in the visual cortex of live ferrets to watch brain-cell responses to visual stimuli. Using high-resolution light microscopy and special dyes that illuminate astrocytes and cell activity, Sur says, “we could tell what the response of a neuron was and how it differed from the response of an astrocyte right next to it.” In the visual system, neurons are finely tuned to different inputs: some detect light and dark edges, for instance, while others detect orientation of an object. Surprisingly, the scientists found that astrocytes were just as specific for certain features as their adjacent neurons, if not more so.

When they administered a drug that blocked astrocytes’ ability to respond to signals from the neurotransmitter glutamate, the increase in blood flow that characterizes the brain’s response to a stimulus disappeared. The finding suggests that astrocytes play an important role as mediator between the chemical signaling of neurons and the resulting flow of blood that brings critical energy to areas with high brain activity. “If you don’t have astrocytes, you don’t get an increase in blood volume,” Sur says. It also shows that increased blood flow is not a direct result of neurons firing but of chemical communication at the synapses between them. Synapses typically have a branch of an astrocyte nearby, either projecting into or wrapping around the synapse. Astrocytes also branch out to nearby blood capillaries. Sur says that astrocytes likely take up neurotransmitters released into synapses and cause nearby capillaries to dilate.

The findings have implications for fMRI, which has been used to illuminate areas of the brain responsible for many thought processes, actions, and emotions. The technique has become a mainstay of neuroscience as the best way to monitor activity in the entire brain noninvasively. But questions have plagued these studies, as it is difficult to know what is happening when a particular part of the brain “lights up” in MRI images. Sur says that it’s important for scientists to be aware that MRI images reflect the status of astrocytes, and that “things that influence astrocytes will influence the signal.”

Sur also believes that astrocytes may play roles in brain function and disease that have yet to be discovered. He is currently investigating whether astrocytes are involved in certain diseases of the brain, as changes in blood flow are seen in Alzheimer’s disease and other brain disorders.

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