Powerful Advancement in Technology Furthers Capacity to Link Brain Activity with Behavior

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Karl Deisseroth, M.D., Ph.D., Expert on brain and behavior research, depression research, optogenetics and clarity
Karl Deisseroth, M.D., Ph.D.

A groundbreaking technology for identifying how brain activity impacts behavior, developed by Brain & Behavior Research Foundation Scientific Council member Karl Deisseroth, M.D., Ph.D., has now become even more powerful.

A decade ago, Dr. Deisseroth, supported by a NARSAD Young Investigator Grant, and his students at Stanford University, introduced optogenetics, a sophisticated technique that enables selective activation of individual brain cells in lab animals to observe the impact on behavior. This remarkable ability to trigger brain-circuit activity with a flash of light has been adopted for use in labs worldwide and is enabling crucial insights into the mechanisms of brain function and how their dysfunction can cause various brain and behavior disorders.

In the current paper, published April 25th in the journal Science, the Deisseroth team announced a new and powerful enhancement of the method that enables researchers to selectively inhibit activity and switch neurons off.  This gives researchers the ability to both activate and inactivate neurons in deep brain structures in live animals and see what the effect on behavior is.

This latest achievement “is the type of neurotechnology envisioned by President Obama when he launched the BRAIN Initiative a year ago,” states Thomas R. Insel, M.D., Director of the National Institute of Mental Health. “It creates a powerful tool that allows neuroscientists to apply a brake in any specific circuit with millisecond precision, beyond the power of any existing technology. This will be vital for understanding brain circuits involved in behavior, thinking, and emotion."

To develop optogenetics, the Deisseroth lab figured out how light-sensitive proteins from algae (channelrhodopsins) could be used in mouse models to stimulate the activity of brain cells with pulses of light. Their initial work was reported in a landmark 2005 paper in Nature Neuroscience. A further formidable challenge for the team proved to be finding a way to transform the channelrhodopsins so that they could also inhibit neural activity and allow for the flip side of interventional brain research.

"This is something we've sought for many years and it's really the culmination of many streams of work in the lab—crystal structure work, mutational work, behavioral work,” explains Dr. Deisseroth. "What had been working through a weak pump [inhibition of neural activity] can now work through a highly efficient channel with orders of magnitude greater sensitivity for impact on cell function."

Read more about this research:

Channel makeover bioengineered to switch off neurons

Researchers build new 'off switch' to shut down neural activity

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