RIKEN Brain Science Institute (RIKEN BSI) RIKEN BSI News No. 10 (Dec. 2000)




How Far Will Brain Science Research Advance and What Will It Bring?

Observing the dynamics of the spine

Mr. Takashi Tachibana (left) and Dr. Masao Ito, Director of the BSI.
A series of interviews conducted by Mr. Tachibana on brain science began with a discussion with Dr. Ito, currently the director of the BSI, who at the time was director of the Frontier Research System. A thought-provoking conversation between the two regarding the frontier of brain science continued for some time.

Tachibana: Substantial progress has been made in the field of biological science as a result of the visualization of gene expression by means of fluorescent materials. Because of the successful visualization of the performance of the brain using fluorescent materials, havenユt there been some unexpected findings?
Ito: Using light is one of the least invasive ways of probing in the brain. Whereas everyone knows the role of the microscope in revealing the morphology of the brain, it is relatively recent that another property of light has come to be widely used. Light can be used to excite molecules to produce a characteristic fluorescence. With modern molecular methods it has become possible to express fluorescent molecules, normally produced by marine animals, in mammalian neurons. This method has been so successful that a world wide search is on for making such molecular markers for more specific processes in the neuron. Such markers can be excited deep in the tissues with the two photon methods.
Tachibana: What do you mean by "two photon excitation"?
Ito: As you know, light is carried by energy particles called photons. The photon energy can also be thought of as the color. Molecules are excited to fluoresce when they capture photons of a certain energy, like ultraviolet light photons. It turns out that if the same molecule captures two photons of one half the ultraviolet energy simultaneously, it receives the same energy as one photon at the ultra violet light. Since the lower energy light is less damaging, it can be used to excite marker molecules signaling what is going on in the neurons below the surface of the brain.
Tachibana: Do you mean in live samples?
Ito: Yes, thatユs right. It is now possible to observe for example, how calcium ions are moving in the neuron as it performs its function or when a neurotransmitter is released at the synapse. Such observations were only hopes and dreams just a few years ago.

Can we analyze language functions?
Tachibana: I have heard that there are several research groups being planned: the communication function research group, the architecture research group and the hardware system research group.
Ito: Yes, and the most difficult one is the communication function research group.
Tachibana: What sort of directions in communications research do you hope to explore in the communication function research group?
Ito: Since the opening of the institute, I have faced many challenges but this one is probably the most difficult. Language, including gestures is one of the most obvious functions of the brain but has not been studied as the other functions such as vision, audition and olfaction.
Tachibana: I have heard that you have recently expanded the cerebellum control model of recognition functions to render it applicable to the language system.
Ito: Yes, as a model.
Tachibana: When I first met you, you told me that conventionally, the cerebellum had been connected with motor functions, but things might have changed, and that the cerebellum could be used in high-level functions including language functions. I now see that your hypothesis is gradually expanding; this is very interesting.
Ito: Yes. The cerebellum is a critically important part of the brain in the control of motor activity of the body and has long been thought to have only this role. However, recent evidence has begun to show that it is also involved in cognitive functions as well. I am particularly interested in how the cerebellum may be involved in language as a model for its involvement in cognitive functions.
Tachibana: These tools have revealed that the cerebellum is actually in operation when we use language.
Ito: We have convincing supporting evidence for this. However, linguistics is difficult. As Chomsky (*4) has said, "Humans have diversified languages; however their grammatical structure is universal". If the universal grammatical structure results from an intrinsic function of the human brain, we cannot approach the linguistic function through studies of the brains of other animals. Usually, we consider that our brains are similar to those of animals, and that they have developed through a process of evolution. Although small, a chimpanzee has a bud in the language area; this same area has expanded in humans. Although researchers have attempted to teach chimpanzees vocal language, all attempts have been unsuccessful.
Tachibana: The reason for this failure is that the anatomical structures required for sound-making, such as the Adamユs apple and the palate, are different from those of humans. Research to demonstrate that chimpanzees, though unable to use vocal languages, are able to use language in the form of sign language or by pointing to symbols on a character board, is in progress. Currently, the analysis of human sign language is being actively pursued. There are standard hand signs and it is evident that sign languages exist. However, in actual sign languages used for practical purposes, people use things in addition to hand signs, such as facial expressions, line of sight, and the acceleration and direction of hand movements. It appears that if only the hand signs are converted into a language, the amount of information which can be conveyed is very small. However, the amount of information practically converted is fairly large. It has been proven that sign language is a very complex form of language. In other words, we began to realize that sign language is an established language system that differs from general languages. Similarly, although animals do not use languages like those of humans, they do have established various means of communication.
Ito: Yes, but Chomsky puts forth that a universal grammar emerged abruptly in the evolution of human language functions. I think by this he implies that a major branching occurred in human evolution which may not have occurred among our nearest animal kin.
Tachibana: Since there is a capacity for communication which is common among animals using general symbol manipulation in a form similar to that of a universal grammar for humans, I wonder if chimpanzees are able to master sign language.
Ito: We would like to explore this particular linguistic door opened by Chomsky at the level of the formation of a universal grammar.

Treatment by means of neural cell transplantation
Tachibana: In the area of protecting the brain, the day on which we conquer Alzheimerユs disease is drawing nearer.
Ito: Very soon, we will have effective medications. A major sign of this disease is the accumulation of the protein b amyloid. The rate of accumulation is very slow so that it takes 10 years before enough is present to be seen with the microscope and a further 10 years before the symptoms of dementia appear. Thus, it requires a total of approximately 20 years for Alzheimerユs disease to become apparent. Therefore, if we can identify the accumulation of b amyloid earlier and administer medication, this disease can be prevented. The number of Alzheimerユs patients is increasing. Currently, the number of sufferers worldwide exceeds 15 million. It occurs commonly and one is considered lucky if he/she is not diagnosed with the disease beyond the age of 100. The number of sufferers is increasing as our society ages. A cure must be found.
Tachibana: Neural cell transplantation, which involves taking some of our own neural cells from the brain, culturing them, and then returning them to the brain, will be effective to a certain extent. Setting aside whether or not such a procedure is possible in the case of Alzheimerユs disease sufferers, the transplantation of neural cells will be applicable in the case of several other brain disorders.
Ito: Yes, by transplanting neural cells in a manner similar to rice planting. The theory underlying neural cell transplantation has been under consideration for a long time.
Tachibana: The technology for the in vitro culturing of neural cells has been improving rapidly. I visited Dr. Eisuke Okanoユs laboratory at Osaka University, and they have developed a technology for culturing neural cells and sorting the cultured cells using a laser beam. When I saw this technology, I envisioned a new world which is completely different than that which we know today.

Inclusion of brain science in the elementary-school curriculum
magnified scene by clicking image
Spine photograph taken by a two-photon laser microscope Fluorescent photographs of a dendrite of a rat neuronal cell and the spine on the surface. Taken using a two-photon laser microscope. (Provided by Dr. Atsushi Miyawaki, Head of the Laboratory for Cell Function Dynamics)
Ito:Following development of the fields of understanding the brain, protecting the brain and creating the brain, a new field has emerged recently, that of nurturing the brain. That is, looking after the development of the brain, or assisting in the normal growth of the brain.
Tachibana: Mechanisms to nurture the brain, or the social mechanism for this, are part of the education system. Since these mechanisms are not functioning well today, I believe that a lot of strange social phenomena occur. What we should do in our education system is change the framework of the science subjects, starting at the elementary-school level. We should include the study of brain science and should teach it as a subject. We should teach the pupils subjects in accordance with those studied here, including those related to understanding, protecting and creating the brain. If this is done properly, the number of outstanding brain scientists will increase. Furthermore, a faculty of brain science should be established in each university. There, people can study various topics, ranging from how the brain is used to how to use the brain, in addition to the creation of the brain and the publication of new findings. When this is realized, the universities thus created will be much more general universities, because brain science covers such a broad range of topics.

The most important issue: understanding the mind
Ito: There are many expectations in the area of creating the brain, yet there are too many unknown parameters. For example, the mechanisms of how we recognize patterns and motion and how to control motion have been analyzed to a certain level. However, when it comes to issues closely related to the mind, we do not know how they work. In the case of emotions such as happiness and sadness, it is likely that threshold values are set for neurotransmitters such as dopamine and adrenaline; when the signal level is higher than the threshold value people are happy, and when the level is lower than the threshold value, people are sad. We can speculate on this topic, but it is very difficult to reproduce situations using a computer or a robot.
Tachibana: The definition of emotion is an important issue.
Ito: Yes, you are right. But we are able to reproduce something like emotion.
Tachibana: Actually, it is very difficult to completely understand our mind and emotions isnユt it?
Ito: If we rely upon subjective experiences, we cannot understand these at all. Nonetheless, we have recently come to understand the brain fairly well; therefore, an increasing number of people believe that we shall be able to understand our mind and emotions fully in the near future. The understanding of our mind and emotions is the most significant issue of the 21st century. I feel that we will be able to make substantial progress.
Tachibana: You wrote somewhere that understanding the brain means understanding everything about human beings, in addition to understanding the many different aspects of humanity including our societies and histories. Furthermore, when we think of the history of the evolution of the brain, all histories of living things are represented by human brains.
Ito: The apex of evolution is the human brain.


Notes:
*1 Frontier Research System
It was established at the Institute of Physical and Chemical Research (RIKEN) in 1986 and is an organization which carries out advanced basic research (frontier research) in unexplored areas globally, intensively and flexibly.
*2 Postdoctoral fellow (postdoc)
Researchers who have received a doctoral degree and are working in a temporary position before assuming a permanent research (educational) position. A trainee with a doctoral degree.
*3 Advanced Technology Development Center
It was established with the aim of advancing research related to the creation of new technologies which can be the basis for brain science research. The responsibilities are divided into research for the development of a new measurement technology and the development of new biological technologies. It includes research resources such as facilities for experimental animals and jointly used devices and equipment.
*4 Chomsky
Noam Avram Chomsky is a Professor of Massachusetts Institute of Technology. Born in the U.S.A. in 1928, he is a theoretical linguist.
Pictures of interviewer by Nariaki Ohnishi
RIKEN BSI NEWS

RIKEN BSI HOME
RIKEN Brain Science Institute (RIKEN BSI)
Copyright All Rights Reserved.