FRET-based Technique Probes Neuron-Astrocyte Proximity
An astrocyte (green) interacts with a synapse (red), producing an optical signal (yellow). Credit: UCLA/Khakh lab
An advance by UCLA neuroscientists could lead to a better understanding of astrocytes, star-shaped brain cells that are believed to play a key role in neurological disorders like Lou Gehrig’s, Alzheimer’s and Huntington’s diseases.
Reported in Neuron, the new method enables researchers to peer deep inside a mouse’s brain and watch astrocytes’ influence over the communication between nerve cells in real time. The test relies on fluorescence resonance energy-transfer microscopy, or FRET microscopy, a technique that uses light to measure the tiniest of distances between molecules.
The UCLA team focused on astrocytes’ relationship with synapses, the junctions between neurons that enable them to signal each other and convey messages. Neuroscientists have tried for years to measure how astrocytes’ tentacles interact with synapses to perform important brain functions. Until now, however, no one had developed a test suitable for viewing adult brain tissue in living mice.
“We’re now able to see how astrocytes and synapses make physical contact, and determine how these connections change in disorders like Alzheimer’s and Huntington’s diseases,” said Baljit Khakh, the study’s lead author and a professor of physiology and neurobiology at the David Geffen School of Medicine at UCLA. “What we learn could open up new strategies for treating those diseases, for example, by identifying cellular interactions that support normal brain function.”
Khakh’s team sent different colors of light through a lens to magnify objects that are invisible to the naked eye. Using FRET microscopy allowed them to see objects about 100 times smaller than would be viewable using conventional light microscopy. As a result, the researchers could observe how interactions between synapses and astrocytes change over time, as well as during various diseases, in mice.
“We know that astrocytes play a major role in how the brain works and also influence disease,” said Chris Octeau, the study’s first author and a UCLA postdoctoral fellow in physiology. “But exactly how the cells accomplish these tasks has remained murky.”
It had been unclear to scientists how often astrocytes make contact with synapses and how these interactions change during disease or as a result of different types of cellular activity. The UCLA advance should enable scientists to address those questions.
“This new tool makes possible experiments that we have been wanting to perform for many years,” said Khakh, who also is a member of the UCLA Brain Research Institute. “For example, we can now observe how brain damage alters the way that astrocytes interact with neurons and develop strategies to address these changes.”
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