Stanford psychiatrist-bioengineer-neuroscientist-inventor Karl Deisseroth, MD, PhD, has pioneered two separate technologies that, while quite different from one another, pose the prospect of working together to enable new strides in brain research.
In a new study in Cell, Deisseroth and his colleagues combined the two methods to gain deep insights into how the brain processes positive versus negative experiences. These insights hold implications for the development of drugs or other therapies to treat drug addiction and mental illnesses.
One of the two technologies developed under Deisseroth’s direction, called optogenetics, involves genetically modifying cells — nerve cells (also known as “neurons”), in this study — of living animals so that the cells’ function (e.g., neurotransmission) can be turned on and off with light.
The other technology, called CLARITY, is a way of removing the fatty, opaque tissues that constitute an intact, non-living brain, leaving behind — astonishingly — a transparent physical replica with the same structure as the original brain and with all of that original’s parts and wiring exactly in place.
In the new study, according to a news release on the study written by freelancer and former colleague Andy Myers, the researchers used CLARITY s to trace specific pathways and “label” specific molecular structures within the brains of their subjects (which, in this case, were mice):
The researchers gave the mice positive or negative stimuli. Only the neurons that had been strongly active during the experience became labeled – along with their outgoing connections – allowing effective tracing of the distinct circuits through the brain.
Now, according to the release:
Using optogenetics, the researchers controlled specific neurons, within the living animals, that had been active during positive or negative experiences. The team was able to then evaluate how those particular neurons affect behavioral outcomes.
By pairing the techniques in the same experiment, Deisseroth’s team was able to determine that the positive-experience-driven neurons in the brain area of interest were different from the “negative” cells not only in their molecular features but also in their wiring: Positive-versus negative-experience-oriented neurons connected to distant places in the brain in fundamentally differing ways.
In an interview for the news release, Deisseroth said the study opens the possibility, in future work, of identifying and targeting different cell types with diverse therapeutic approaches, including drugs or external stimulation techniques.
Previously: Daedalus, or Icarus? A small set of nerve cells in the brain determines risk-preference settings, Hyperactivity in the brain’s “self-control” center may stifle the pleasure-seeking urge, Party animal: Scientists nail “social circuit” in rodent brain (and probably ours, too) and Peering deeply – and quite literally – into the intact brain: A video fly-through
CLARITY image — which show neural connections from the prefrontal cortex across an entire transparent mouse brain — courtesy of Li Ye and Karl Deisseroth