Karl Deisseroth to share Horwitz Prize for pioneering contributions to optogenetics

The Stanford psychiatrist, neuroscientist and engineer is honored for developing a technology that lets researchers pinpoint the functions — and malfunctions — of specific brain circuits.

- By Bruce Goldman

Karl Deisseroth

Karl Deisseroth, MD, PhD, the Stanford Medicine D.H. Chen Professor as well as a professor of bioengineering and of psychiatry and behavioral sciences, has been named a recipient of the 2022 Louisa Gross Horwitz Prize for his foundational contributions to the advancement of optogenetics, a technology that has transformed neuroscientific research.

The Horwitz Prize has been awarded annually by Columbia University since 1967 for groundbreaking work in medical science. Of the 108 previous Horwitz Prize winners, 51 have gone on to receive Nobel prizes.

Deisseroth, who is a Howard Hughes Medical Institute investigator, will share the prize — to be presented at a ceremony in New York on Feb. 16, 2023 — with two other pioneers in the field: Peter Hegemann, PhD, professor of neuroscience at the Institute of Biology and Experimental Biophysics at the Humboldt University of Berlin; and Gero Miesenböck, MD, professor of physiology at the University of Oxford, UK.

“The Horwitz Prize has a long, distinguished history, and this year it recognizes Karl Deisseroth’s outsized contributions that forged the field of optogenetics,” said Lloyd Minor, MD, dean of the Stanford School of Medicine. “His research has led to significant advances in neuroscience that enable greater understanding of the inner workings of the human brain and are helping to address a wide range of neurological conditions.”

Hegemann, Deisseroth’s longtime collaborator, initially identified channelrhodopsins: natural proteins derived from single-celled microbes that respond to light by allowing ions to flow across cell membranes. Deisseroth discovered and designed new classes of channelrhodopsins, described the first high-resolution structures of the three major types of channelrhodopsins, and pioneered a revolutionary new use for these proteins. He and colleagues found a way of situating them on selected neurons’ outer membranes and then, by conveying light pulses from a distance, inhibiting or activating impulse transmission selectively in those neurons.

This technique, known as optogenetics, has revolutionized the study of how brain circuits in living mammals interact to produce behavior. It lets neuroscientists selectively, quickly and accurately activate or inhibit just the cells or circuits they’re curious about. They can even find out what that particular neuron or circuit is doing in a living animal’s brain.

Before the advance of optogenetics, there were two main experimental workhorses for studying the brain: electrical stimulation and drugs. Exciting neurons, or nerve cells, by stimulating them with jolts of electricity elicits an immediate response. But it’s imprecise: It also trips off responses in neighboring brain cells and circuits other than the one being studied. Worse, while electrical stimulation can activate neurons, it can’t precisely inhibit them, which is critical to studying brain function.

Drugs are also imprecise. They can selectively activate or inhibit neurons — but not necessarily just the ones in the circuit of interest. Plus, they diffuse widely and can’t be mopped up quickly, making them poor on/off switches.

Deisseroth has freely distributed his optogenetic tools and trained thousands of scientists from around the globe in putting optogenetics to work. Numerous researchers — including Deisseroth — have used the technology to study learning, memory, perception, motivation, mood and appetite, and to detect neural-circuit deficiencies causing or exacerbating Parkinson’s disease, schizophrenia, autism, anxiety, depression, addiction and other conditions.

In one instance, scientists have even used optogenetics directly to help a blind person see. But Deisseroth said he envisions optogenetics’ major clinical applications to be more broad and general.

“We can use this tool to better understand what causes all kinds of neurological and psychiatric disorders, which will accelerate clinical progress toward a broad spectrum of treatments for them,” he said.

Last year, Deisseroth was a co-recipient of the Lasker Basic Medical Research Award for his development of optogenetics and for fundamental discoveries regarding channelrhodopsins’ principles of function.

Previous Stanford Medicine recipients of the Horwitz Prize include structural biology professor Roger Kornberg, PhD, in 2006, and developmental biology professor Lucy Shapiro, PhD, in 2012. Kornberg also won the Nobel Prize in chemistry in 2006.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu.

2023 ISSUE 3

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