Flavio Donato Wins 2017 Eppendorf & Science Prize

Flavio Donato in front of an ultrasound machines used to guide viral injections into the developing mouse brain. | Rita Elmkvist Nielsen, Norwegian University of Science and Technology, Kavli Institute for Systems Neuroscience

Flavio Donato has been named the 2017 grand prize winner in the annual international competition for The Eppendorf & Science Prize for Neurobiology. Curious about the brain's "instruction manual" during development, Donato sought to make sense of how the brain's components work together to form a highly functional organ.

"We must start applying the same technologies developed for the study of adult circuits to developing circuits, so that researchers can successfully examine how function emerges from the fascinating orderly mess that is the brain during the first weeks of life. Only by integrating the investigation of neural circuit assembly, structure and function can we then really have a chance to comprehend how the brain as a whole gives rise to those sophisticated phenomena that make us who we are," Donato said.

For decades, it has been well established that for parts of the brain to mature and establish the specific connections that make cognition possible, waves of neural activity must spread from the eyes, ears, and nose to the center of the nervous system, the brain's sensory cortical areas. Sensory experience in young animals is instrumental in this phenomenon, and the sensory organs are the source of this developmental signal.

Seeking additional insight into similar mechanisms at work in other centers of the brain, Donato and his team discovered that the signal to develop one area known to be involved in more abstract functions, including memory and navigation, originated from deep within the brain, in a specific population of neurons that kicks off the maturation of an entire neural network. Interestingly, those cells seemed to be intrinsically programmed to perform this operation, since their own maturation likely depended on a clock that started ticking the moment they developed. When Donato's team silenced the neurons, the part of the brain known to function in memory and navigation, called the entorhinal-hippocampal region, did not develop properly.

Researchers have good methods for labeling neurons based on where in the brain they developed, but the methods for labeling neurons that develop at the same time are less precise. To remedy this, Donato pioneered a strategy that allowed his team to find the neurons responsible for building the entorhinal-hippocampal region targeted toward the developing brains of mice at specific time points. The technique allowed him to zero in on and label populations of neurons that develop at the time of labeling, without any previous understanding about their identity beyond their birthdate. Donato emphasized that this labeling step was key to closely tracking development among a crowd of neurons, in addition to manipulating their activity at later stages of life.

"These experiments opened up a new world to us," Donato said. "By observing entorhinal-hippocampal neurons based on their birthdate, we realized that these cells were somehow special and very different from the other surrounding cell types, which was instrumental to find out how and to what extent they influenced the assembly of the network."

Donato's prize-winning essay , "Assembling the brain from deep within," highlights how his results have important implications in degenerative brain disorders such as Alzheimer's disease. "Many neurological conditions seem to target specific populations of neurons that are more susceptible than others to molecular events underlying the pathology," he wrote. "In the case of Alzheimer's disease, one of the first cell types affected by the pathology is one that we've observed to play a leading role in the development of the entorhinal-hippocampal network." Donato believes that further investigation may someday give scientists the ability to "slow down or even rescue the deficits that such pathologies produce in the brain."

Knowing how these cells mature during development might lead to a better grasp of just how to replicate that process in the adult brain, which could eventually pave the way to strategies that rejuvenate aging circuits, Donato said.

"Flavio Donato investigated a critical aspect of circuit maturation in the developing brain," said senior Science editor Peter Stern. "It was his well-written essay, the high quality of his research, and his meticulous attention to detail that helped him win this year's prize."

Donato, who is currently completing his postdoctoral fellowship at the Norwegian University of Science and Technology, said next steps will involve delving into the "early-life dynamics necessary for the production of circuits that represent space in the brain, and help humans create memories of life's everyday events."

Donato and the following finalists will be recognized at a prize ceremony in conjunction with the Annual Meeting of the Society for Neuroscience. The ceremony will be held at Science/AAAS Headquarters in Washington D.C. on November 12.

· Viviana Gradinaru, for her essay "Overriding sleep." Gradinaru received her undergraduate degree from the California Institute of Technology and her Ph.D. from Stanford University. Now an assistant professor at Caltech, Gradinaru and her research group are developing technologies for neuroscience, including optogenetics, tissue clearing, and viral vectors, and using them to probe circuits underlying locomotion, reward, and sleep.

· Graham Diering, for his essay "Sleep on it." Diering received his bachelor's and doctorate degrees at the University of British Columbia. As a postdoc at Johns Hopkins University, Diering characterized changes in synapse composition that occur during sleep. Now an assistant professor at the University of North Carolina, Chapel Hill, Diering's laboratory focuses on the role of sleep in neural development.

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[Credit for related image: Alan Simpson/ Flickr]