The Kavli Prize in Neuroscience is shared between Eve Marder, Brandeis University, USA, Michael Merzenich, University of California San Francisco, USA, and Carla Shatz, Stanford University, USA. They receive the prize “for the discovery of mechanisms that allow experience and neural activity to remodel brain function”.
From left: Eve Marder, Brandeis University, USA; Michael Merzenich, University of California San Francisco, USA; Carla Shatz, Stanford University, USA.
Keeping the old tricks and learning new ones: how the brain remains stable yet flexible
Until the 1970s, neuroscientists largely believed that by the time we reach adulthood the architecture of the brain is hard-wired and relatively inflexible. The ability of nerves to grow and form abundant new connections was thought mainly to occur during infancy and childhood. This view supported the notion that it is easier for children to learn new skills such as a language or musical instrument than it is for adults. Over the past 40 years, however, the three Kavli neuroscience prize-winners have challenged these assumptions and provided a convincing view of a far more flexible adult brain than previously thought possible — one that is ‘plastic’, or capable of remodeling. Working in different model systems, each researcher has focused on how experience can alter both the architecture and functioning of nerve circuits throughout life, given the right stimulus and context. They have provided a physical and biochemical understanding of the idea of ‘use it, or lose it’. This new picture of a more adaptable brain offers hope for developing new ways to treat neurological conditions that were once considered untreatable.
Michael Merzenich demonstrated that sensory circuits in the cerebral cortex can be reorganized by experience in adulthood. Different parts of the body are represented in a continuous map in the somatosensory cortex. After demonstrating reorganization of this map after injury, Merzenich showed that simply expanding or limiting the use of different fingers leads to a corresponding change in the representation of the hand in the brain. Similarly, he showed that the auditory cortex can change its map of sound frequencies after individuals are trained to detect fine differences in pitch. This discovery helps explain how humans can recover their perception of speech with electronic cochlear implants, which generate signals much simpler than normal auditory inputs. Merzenich showed that neuromodulators as well as cognitive factors including attention determine whether adult plasticity takes place. This work is being extended in humans to maximize learning and recovery from brain injury and disease.
Carla Shatz showed how patterns of activity in the developing brain instruct and refine the arrangement of synapses between neurons. She demonstrated that the formation of appropriate connections between the eye and the brain of mammals depends on neuronal activity before birth. She discovered that spontaneous waves of activity sweep across the retina early in development, and showed that these organized activity patterns select the final set of connections from a coarse, genetically-determined map. Her demonstration that “neurons that fire together, wire together” links the mechanisms of brain wiring during development to those underlying adult learning and memory.
Eve Marder used the simple circuits of crustaceans to elucidate the dynamic interplay between flexibility and stability in the nervous system. She showed that numerous neuromodulators reconfigure the output of adult neural circuits without altering their underlying anatomy. At the same time, she found that circuits can generate similar neuronal and network outputs from many different configurations of intrinsic neuronal excitability and synaptic strength. This apparent paradox was solved by her recognition that neurons have a self-regulating homeostatic programme that drives them to a stable target activity level. With the other two Kavli Prize laureates, Marder defined the mechanisms by which brains remain stable while allowing for change during development and learning.
Illustration showing the action of neurotransmitters such as serotonin and noradrenaline in the synaptic cleft. Vesicles containing the neurotransmitter (green) move towards the pre-synaptic membrane where they fuse with the cell membrane, releasing their contents into the synaptic cleft. The neurotransmitter molecules act on the post-synaptic cell by binding to specific receptors on the cell surface (purple). They can also be taken back up by the presynaptic cell via other receptors (orange) for re-use. (Credit: Arran Lewis, Wellcome Images)
About the Kavli Prizes
The Kavli Prize is a partnership between the Norwegian Academy of Science and Letters, The Kavli Foundation (USA) and the Norwegian Ministry of Education and Research. The Kavli Prizes were initiated by and named after Fred Kavli (1927-2013), founder of The Kavli Foundation, which is dedicated to advancing science for the benefit of humanity, promoting public understanding of scientific research, and supporting scientists and their work. Kavli Prize recipients are chosen biennially by three prize committees comprised of distinguished international scientists recommended by the Chinese Academy of Sciences, the French Academy of Sciences, the Max Planck Society, the U.S. National Academy of Sciences and the Royal Society. After the prize committees have selected the award recipients, their recommendations are confirmed by the Norwegian Academy of Science and Letters.
The 2016 Kavli Prizes will be awarded in Oslo, Norway, on 6 September. His Royal Highness Crown Prince Haakon will present the prizes to the laureates. This year’s ceremony will be hosted by Alan Alda and Lena Kristin Ellingsen. Prime Minister Erna Solberg will host a banquet at Oslo City Hall in honour of the laureates. The ceremony is part of Kavli Prize Week – a week of special programmes to celebrate extraordinary achievements in science. Prize lectures and symposia in neuroscience and nanoscience will be held in Trondheim on 8 September.