Last month, Stanford's Karl Deisseroth, MD, PhD, and colleagues in his lab sparked excitement among the scientific community and general public after announcing their development of CLARITY, a process that renders tissue, specifically a mouse brain, transparent. But this wasn't the first time Deisseroth garnered attention for his work pioneering a blockbuster brain technique. He dedicated a significant portion of this century’s first decade to creating a revolutionary method for studying the brain called optogenetics.
A lengthy Nature feature published yesterday offers an in-depth look at Deisseroth's rise from "persistent and persuasive" PhD student to "a major name in science," and his development of two paradigm-shifting methods. In the piece, writer Kerri Smith explains how a residency in psychiatry set him on his current path:
“Everything changed when I did my psychiatry rotation,” says Deisseroth. “A person can be right in front of you who looks intact, not obviously injured, and yet their brain is constructing for them a completely different reality. At the same time I saw how deep the suffering was.”
Studying depression or anxiety in a dish of cells was inadequate, he reasoned, because only whole brains can give rise to the sophisticated functions — and disorders — that characterize human behaviour. And techniques for studying whole brains in humans and model organisms were often limited to simply watching them at work.
So Deisseroth began thinking about ways to examine and control intact systems. “I was having a lot of discussions with a lot of people,” he says. During his residency, Deisseroth met [Edward] Boyden, a PhD student with similarly ambitious aims. The two began talking about ways to manipulate individual neurons as a side project. “It was a very adventurous collaboration, full of exploration,” says Boyden.
One idea involved using light to control neuronal firing. Boyden and Deisseroth knew about light-sensitive channel proteins called opsins, which algae use for generating energy, among other functions. Several groups — including ... [Roger Tsien, PhD,] at the University of California, San Diego — were trying to insert these proteins into neuron cell membranes. The project needed “the wherewithal to spend the money and find the graduate students”, says Deisseroth. In 2004, having secured his own lab, he could do just that.
The feature also includes two podcasts of Deisseroth discussing his work.
Previously: Peering deeply – and quite literally – into the intact brain: A video fly-through, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, Researchers induce social deficits associated with autism, schizophrenia in mice, Anti-anxiety circuit found in unlikely brain region and Nature Methods names optogenetics its “Method of the Year
Photo by Linda Cicero/Stanford News Service