Neuroscience Research: Before and After the Evolution of Optogenetics

Abstract In an article titled “Thinking about the Brain,” published in a special issue of Scientific American devoted to the Brain in September 1979, Francis H.C. Crick wrote: “Reflecting on itself, the human brain has uncovered some marvelous facts. What appears to be needed for understanding how it works is new techniques for examining it and new ways of thinking about it.” He made several important observations about the technological limitations of the time, noting that electrodes cannot readily distinguish different types of neurons. Light could be an ideal signal to turn firing on and off in an alert animal (Crick 1999; Crick 1979). This conceptual blueprint was eventually realized experimentally through the groundbreaking work of Hegemann, Nagel, Deisseroth, and their colleagues, who harnessed the microbial channelrhodopsins to achieve fast, genetically targeted, light-driven control of neuronal activity (Boyden et al. 2005; Nagel et al. 2002; Nagel et al. 2003). Over the past two decades, optogenetics has become a mainstay of circuit neuroscience and is now emerging as a potential therapeutic approach. In light of the 2026 Nobel Prize awarded to optogenetics, this perspective narrates the evolution of neuroscience research before and after the advent of optogenetics, and summarizes how this technology has transformed our approaches to studying the brain.