rman of the board of the Warren Alpert Foundation and former dean of Harvard Medical School.
Light, molecule, action!
The advent of optogenetics and the subsequent advances in the field stem from the collective work of many scientists over nearly two decades. However, the four award recipients made the essential discoveries that set the stage for using this approach and enabled researchers to manipulate neurons via genetic modification and light stimulation.
The tantalizing yet far-fetched idea of using light to modify neuronal activity became a reality in 2002 when experiments conducted by Miesenböck demonstrated that it was, indeed, possible to do so. He developed light-sensitive signaling pathways into molecular tools to probe neuronal function at the cellular and systems levels. Miesenböck tested the approach in a living organism--the fruit fly--and demonstrated for the first time that it is possible to use light to control the brain, offering a new way to illuminate its function.
Miesenböck genetically incorporated light-detecting proteins derived from the eyes of flies--light-sensing molecules called rhodopsins--into nerve cells. This achievement did not merely render neurons sensitive to light but also offered a way to control their activity remotely. The outer membrane of these modified neurons was studded with light-activated channels that could control the flow of electric and chemical signals into and out of the cell. This feature allowed scientists to turn the neurons on and off simply by exposing them to light. When a flash of light hits one of these molecular channels, the channel opens up, an electrical current is switched on and the neuron fires, activating the circuit in which it resides.
Another pivotal development in the field of optogenetics came from Hegemann, whose efforts spanning decades were initially focused on understanding how green algae sense light. In the 1980s, Hegemann began exploring how the light-activated molecules in green algae and other simple organisms sense light. Starting in the 1990s, Hegemann and his team identified and molecularly characterized the light-activated molecules in these organisms that allow them to respond to light. Known as channelrhodopsins, these molecules and their engineered derivatives are now ubiquitously used by neurobiologists to turn neurons on and off. Hegemann along with Karl Deisseroth deciphered the key principles of light-sensitive channel structure and function.
Deisseroth conducted critical experiments showing the rhodopsin proteins first studied by Hegemann in single-cell organisms could be used to activate neurons. Deisseroth and his team--which also included CRISPR pioneer Feng Zhang-- then discovered that the mammalian brain had the necessary chemicals to make these proteins functional and developed the viral and optical methods to enable study of behavior. Deisseroth's team also developed both optogenetic excitation and inhibition of neurons, achieved the first single-cell-resolution optogenetic control of neuronal activity and behavior in living mammals, and deciphered along with Hegemann the key principles of light-sensitive channel structure and function.
Boyden collaborated on critical early experiments underlying optogenetics, and was part of the team--alongside Zhang, Deisseroth and colleagues--that in 2005 published the discovery that the light-gated ion channels from algae previously studied by Hegemann could be used to control neuronal firing. Boyden went on to further develop optogenetics in his own laboratory. He designed light-sensitive proteins to inhibit, rather than to merely promote, the activity of neurons. He further refined optogenetic activators to allow independent control of multiple cells types in the brain. Furthermore, collaborating with pioneers in holographic microscopy, Boyden developed tools to exploit optogenetics as a way to imprint exact patterns of electrical activity on small groups of neurons, mimicking the natural firing.
Thus, the collective work of the four scientists has made optogenetics a ubiquitous to