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Exploring new horizons of cerebellum research

Masao Ito, founder of the RIKEN Brain Science Institute (BSI), is famous as one of the pioneers in a research movement that has shed light on the deeper functions of the cerebellum. Ito recounts the story of this research in his own words.

The cerebellum is a region of the brain with a curious history. Most well known for its role in motor control, the cerebellum is today known to be involved in everything from cognition to emotion and language. Masao Ito, founder of the RIKEN Brain Science Institute (BSI), is famous as one of the pioneers in a research movement that has shed light on the deeper functions of the cerebellum.

It was to commemorate Ito’s great contributions to brain science that the BSI hosted “The New Horizon of Cerebellar Research” symposium on 29 March 2010, featuring leading scientists discussing their latest findings on the cerebellum. Each from a different perspective, the presenters painted an intricate picture of cerebellar function and its complex relation to cognition.

Richard Ivry of the University of California, Berkley introduced this picture with a review of many decades of research, establishing the cerebellum’s involvement in a range of cognitive functions. Peter L. Strick of the University of Pittsburgh supplied evidence for this involvement through his studies using virus-tracing technology, which confirm the conception that the cerebellum is made up of functional modules each communicating along parallel channels with areas of the cerebral cortex.

On more conceptual ground, Chris Miall of the University of Birmingham identified a strong cerebellar role in the forward modeling and prediction of outcomes. This predictive model was given a more tangible form by Mitsuo Kawato of the Advanced Telecommunications Research Institute, whose group explores internal models of the cerebellum through robot experiments.

In his own presentation, Ito recalled his nearly 50 years of experience researching the cerebellum, stressing the importance of evolution in understanding the brain’s capacity to handle movement and knowledge through common mechanisms. For his many years of tireless work, Ito was rewarded with a standing ovation by the audience in attendance, many of whom have built careers on the basis of his pioneering research. Ito recounts the story of this research in his own words below.

Unlocking the secrets of the cerebellum: a message from Masao Ito

What is it about the cerebellum that so many researchers—including myself—find so fascinating? The answer is to be found in the many mysteries it promises to resolve. The brain is filled with intricate neuronal circuits, but the relatively simple, precise and geometrically exquisite circuits of the cerebellum are particularly intriguing. Those of us who study the brain believe that the cerebellum may provide the clues we need to attain our long-standing objective to decipher the meaning of the brain’s neuronal circuits. To do so would utterly transform our understanding of brain function.

The era in which I began my career in neuroscience, in the 1960s and 1970s, was one that saw rapid advances in this area of research. Neuronal circuits of the cerebellum were dissected in great detail, and the revolutionary Marr–Albus network models, today’s most widely accepted theories of cerebellar function, were first proposed. I made my debut in this field with the finding that Purkinje cells, a class of large neurons in the cerebellar cortex, are inhibitory in nature. The title of the monograph where this finding was reported, “The Cerebellum as a Neuronal Machine” (Eccles, Ito and Szentagothai, 1967), conveys a sense of the spirit of that era.

These discoveries were followed by many more. Our group obtained the first evidence that Purkinje cells are equipped with a type of synaptic plasticity called long-term depression, which depresses the action of synapses that cause erroneous movement. Complex molecular processes underlying synaptic plasticity were also uncovered, and models of the functional modules that make up the cerebellum advanced to the extent that they are today successfully employed to reproduce learning of motor skills in robots.

A number of unexpected findings were also uncovered along the way. Among these is the discovery that only 3% of the 175,000 excitatory synapses on a single Purkinje cell are actually functional. This suggests that while all synapses are initially functional, the majority become long-term depressed through learning, the functional remainder being sufficient to form a specific receptor field for each Purkinje cell.

Another great surprise was the discovery, spotlighted at the New Horizon of Cerebellar Research symposium, that the involvement of the cerebellum may go beyond motor control, to higher-level cognitive functions. Evidence for this involvement is found in a relatively recent evolutionary development, a region of the cerebellum that forms a loop connection with the headquarters of cognitive function—the cerebral prefrontal cortex. Many brain-imaging studies have since revealed that activation of the cerebellum is associated with non-motor cognitive activities such as language.

These discoveries demand that we reevaluate the long-standing dogma of the cerebellum to incorporate not only motor control, but also cognition. Furthermore, it is in learning that we find evidence for a connection between these two types of brain function: repetition of a particular pattern of thought enables us to learn the pattern and reproduce it intuitively, without conscious effort, just as we learn to execute patterns of movement without knowing in detail the motor control mechanisms involved. Many important cognitive functions, including language, intuition, inspiration and giftedness, can be attributed in this way to learning capabilities of the cerebellum.

The connection above suggests the possibility of a common mechanism underlying both motor control in the physical domain, and manipulation of knowledge in the mental domain. The implications of such a mechanism would be profound, touching on a fundamental proposition in science dating back to the time of Descartes that our physical brain embodies the conscious mind. The cerebellum thus holds the key to one of the innermost secrets in science, and one of the greatest mysteries of the brain.

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