Public Release: 

Prize-winning research helps reveal how the brain is built

Flavio Donato honored for uncovering neuron circuit development

American Association for the Advancement of Science

Washington, D.C. - 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 components that make up the brain work together to form a highly functional organ.

His analysis of neuron development offers an entry point into better understanding the organization of the brain, which can help trace back the precise elements of a network that all come together to produce cognition.

For decades, it has been well established that for parts of the brain to mature and establish the specific connections which make cognition possible, waves of activity must spread from the periphery (the eyes, ears, and nose, for example) to the center of the nervous system (the sensory cortical areas). Sensory experience in young animals was revealed to be instrumental for this phenomenon, and the sensory organs were the source of this signal.

Seeking additional insight into the mysterious mechanisms at work in other centers of the brain, Donato and his team discovered that in one of the areas specifically known to be involved in more abstract functions including memory and navigation - the signal source originated from deep within the brain, in a specific population of neurons that kicks off the maturation of an entire 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 were born. Donato found that the activity of these cells was important; when his team silenced the neurons, the part of the brain known as the entorhinal-hippocampal region did not develop properly.

While good approaches to label neurons based on where or from which progenitor they were born currently exist, methods to genetically label cells born at the same time rely only on previous knowledge of the genetic programs defining cell identity. Here, Donato pioneered a novel strategy in the form of a single injection into the developing brains of mice at specific time points. The technique allowed him to zero in on and "label" populations of neurons born at the time of injection, 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 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."

"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.

Donato's prize-winning essay, "Assembling the brain from deep within," highlights how his results have important implications in degenerative brain disorders like 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. 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." He believes that further investigation may someday allow 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, which could eventually pave the way to strategies that rejuvenate aging circuits.

"Flavio Donato investigated a critical aspect of circuit maturation in the developing brain," said senior Science editor Dr. 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 said his 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."

Flavio 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 Sunday evening, November 12, 2017.

2017 Grand Prize Winner

Flavio Donato, for his essay "Assembling the brain from deep within." Donato received his undergraduate degree from the Sapienza University of Rome, and his Ph.D. from the University of Basel. Dr. Donato is currently completing his postdoctoral fellowship at the Norwegian University of Science and Technology, where he studies how internally generated network dynamics in the developing cortex support the periodic firing of neurons that represent space in the brain.

Finalists 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, Dr. Gradinaru and her re-search 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, Dr. Diering characterized changes in synapse composition that occur during sleep. Now an assistant professor at the University of North Carolina, Chapel Hill, Dr. Diering's laboratory focuses on the role of sleep in neural development.

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For the full text of finalist essays and for information about applying for next year's awards, see the Science Web site at http://www.sciencemag.org/prizes/eppendorf.

About Eppendorf AG

Eppendorf is a leading life science company that develops and sells instruments, consumables, and services for liquid handling, sample handling, and cell handling in laboratories worldwide. Its product range includes pipettes and automated pipetting systems, dispensers, centrifuges, mixers, spectrometers, and DNA amplification equipment as well as ultra-low temperature freezers, fermentors, bioreactors, CO2 incubators, shakers, and cell manipulation systems. Consumables such as pipette tips, test tubes, microliter plates, and single-use bioreactor vessels complement the range of highest-quality premium products.

Eppendorf products are most broadly used in academic and commercial research laboratories, e.g., in companies from the pharmaceutical and biotechnological as well as the chemical and food industries. They are also aimed at clinical and environmental analysis laboratories, forensics, and at industrial laboratories performing process analysis, production, and quality assurance.

Eppendorf was founded in Hamburg, Germany in 1945 and has about 3,000 employees worldwide. The company has subsidiaries in 26 countries and is represented in all other markets by distributors.

About AAAS

The American Association for the Advancement of Science (AAAS) is the world's largest general scientific society and publisher of the journal Science as well as Science Translational Medicine, Science Signaling, a digital, open-access journal, Science Advances, Science Immunology, and Science Robotics. AAAS was founded in 1848 and includes nearly 250 affiliated societies and academies of science, serving 10 million individuals. Science has the largest paid circulation of any peer-reviewed general science journal in the world. The non-profit AAAS is open to all and fulfills its mission to "advance science and serve society" through initiatives in science policy, international programs, science education, public engagement, and more. For the latest research news, log onto EurekAlert!, the premier science-news Web site, a service of AAAS. See http://www.aaas.org.

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