New method enables long-lasting imaging of rapid brain activity in individual cells deep in the cortex

As you are reading these words, certain regions of your brain are displaying a flurry of millisecond-fast electrical activity. Visualizing and measuring this electrical activity is crucial to understand how the brain enables us to see, move, behave or read these words. However, technological limitations are delaying neuroscientists from achieving their goal of improving the understanding of how the brain works.

Scientists at Baylor College of Medicine and collaborating institutions report in the journal Cell a new sensor that allows neuroscientists to image brain activity without missing signals, for an extended time and deeper in the brain than previously possible. This work is paving the way to new discoveries on how the brain functions in awake, active animals both those that are healthy and those with neurological conditions.

The holy grail of neuroscience

“Not only is the brain’s electrical activity very fast, it also involves a variety of cell types that have different roles in brain computations,” said corresponding author, Dr. François St-Pierre, assistant professor of neuroscience and a McNair scholar at Baylor. He also is an adjunct assistant professor of electrical and computer sciences at Rice University. “It has been challenging to figure out how to noninvasively observe the millisecond-fast electrical activity in individual neurons of specific cell types in animals carrying on an activity. To be able to do this has been the holy grail of neuroimaging.”

There are existing technologies to measure electrical activity in the brain. “For example, electrodes can record very fast activity, but they cannot tell what type of cells they are listening to,” St-Pierre said.

Researchers also are using fluorescent proteins that respond to calcium changes associated with electrical activity. These changes in fluorescence can be followed using a 2-photon microscope. “This kind of sensor is excellent to determine which neurons are active and which are not. However, they are very slow. They measure voltage changes indirectly, thereby missing a lot of key signals.”

The goal of St-Pierre and his colleagues was to combine the best of these methodologies — to develop a sensor that can monitor activity in specific cell types while capturing fast brain signals. “We have achieved this with a new generation of engineered fluorescent proteins called genetically-encoded voltage indicators or GEVIs,” St-Pierre said.

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