The 56th NIBB Conference, $B!H(BNeocortical Organization$B!I(B, March 12-14, 2010
First, to Professor Yamamori and his Staff
Kenneth Harris expressed what must be the view of many of the participants: $B!H(BThank you for inviting us to the most exciting scientific symposium I have ever attended.$B!I(B The young people in the audience should prepare for disappointment at future scientific gatherings, for few will be as stimulating, with discussion as interesting, as this one.
For all this, we must thank Professor Yamamori: for his wisdom in selecting the participants, for the thoughtful organization of the meeting, and for the wonderful hospitality.
We must all be grateful to be doing neuroscience at this exciting time, when the tools of biology are finally becoming adequate to address the questions we ask.
In many cases, as talks here described, we no longer just present data for everyone to appreciate and try to assimilate. Instead, we can tell stories that really explain important phenomena in neuroscience, where the evidence comes from a variety of approaches. We no longer define ourselves just by our technology, but by the problems we solve.
The new tools for genetic manipulation, for the monitoring of gene expression in select populations of neurons, for brain and cellular imaging, for multi-site micro-electrode recording, for routine high-throughput physiology and anatomy, and for the creation of virtual reality environments as stimuli, change everything. The occasional or anecdotal observation of a decade ago is replaced by quantitative comparisons of significant, large populations.
How different things are from a decade or two ago! I recall another symposium in Okazaki 10 years ago, in 2000, organized by the National Institute of Basic Biology and, 10 years before that, the Cold Spring Harbor Symposium on Quantitative Biology, which brought together many of the world$B!G(Bs best neuroscientists in 1991. Then, the leading edge of the new neuroscience that attempted to synthesize molecular with systems approaches had great promise but little product. How different from the current situation!
Perhaps the greatest change that we see now is the expectation that the tools of molecular biology will be applied wherever appropriate, not just in flies and worms, and not even just in mice, but in primates as well. Particularly for questions of development and plasticity, the convergence of molecular and cellular with systems neuroscience has brought enormous benefits, and promises even more. Most questions even at the highest level of systems neuroscience, such as object recognition, are fundamentally just as much questions of plasticity, the learning that must underlie recognition, as they are questions of representation. Plasticity studies will increasingly benefit from molecular approaches. The role of molecular tools in studying representation is, at this point, much less clear.
The current state of neuroscience in Japan is truly impressive to the visitor. Twenty to forty years ago, Japan had a tradition of tremendous strength in hard-core cellular neurophysiology, with a large fraction of the world$B!G(Bs greatest masters of the micropipette in these islands. As a student and young professor in the 1970s, it was a great honor to meet the leading figures of previous generations, whose papers in the Journal of Physiology and the Journal of Neurophysiology we had all read. And at the other end of neuroscience, those young men Keiji Tanaka and Yasushi Miyashita were leading the field of what we now call cognitive neuroscience. But in between, neuroscience in Japan was very divided into departments of anatomy, biochemistry, physiology, neurophysiology, and genetics that did not talk to one another, and were therefore not doing work nearly as good as they could have done.
Now, if this symposium is a guide, things have changed. Japanese labs, like the best Western labs, are bringing all the relevant approaches together, no longer confining themselves to traditional techniques following the names of their departments.
What are some of the themes of the work we heard over the past 3 days?
One is development of specific cell types and cortical areas. Only a few years ago, we had no taxonomy of cortical excitatory neurons more advanced than that of Cajal and Lorente de No, 60 years earlier. We did have Dr. Kawaguchi$B!G(Bs pioneering taxonomy of inhibitory interneurons, and exploiting this aspect of specificity was tremendously productive in many labs around the world. Now, John Rubenstein presented his dissection of signaling mechanisms for cortical arealization; Dr. Osumi presented information about the early specification of cortical neurons; and Jeff Macklis and Dr. Kawaguchi their work on the subdivision of cell types according to their projections. The important thing about all of this work is that it is not merely descriptive, but it gives us the tools to manipulate cortical development and cell type to do further functional experiments. Who would have dreamed 10 years ago that we would now be at this point?
The mechanisms for the formation of maps and specific connections among cells was the theme of presentations by Drs. Mori and Sur. The interaction between molecular signaling and neural activity in the olfactory and visual systems had amazing parallels in the presentations by Dr. Sakano and me. Again, our understanding of these phenomena is light years beyond what we would have imagined possible only a short time ago.
The mechanisms that underlie specific critical periods of plasticity was the theme of presentations by Drs. Hensch, Tsumoto, and Yoshimura. Phenomena in a number of very diverse systems are coming together using the new technologies now available.
The principles of orchestrated activity in the cortex must necessarily require the study of the simultaneous activity of many neurons, and of connections among multiple distinct areas. Drs. Harris and Kennedy gave us insight into some of the principles of this organization.
The differences among cortical areas was a theme of many talks. No longer need we stop with Brodmann and the areas delineated by neuroanatomists of 50-100 years ago. Dr. Yamamori showed us cortical-area-specific genes that we could never have appreciated from studies of rodents, because some of them are expressed only in the primate cortex. We have for many years appreciated that wonderful things go on in inferotemporal cortex to carry out object recognition. But no amount of anecodatal description of the past could have the impact of Dr. Fujita$B!G(Bs presentation showing that IT cells receive 10 times as many inputs as the cells of V1. Cortexes may seem similar among areas, but at some point quantitative differences become qualitative. Dr. Tanifuji$B!G(Bs quantitative analyses of IT functional organization are a welcome addition to the qualitative descriptions that have been our only earlier guide. The richness of temporal lobe object representation is enhanced by color, as Dr. Komatsu showed. And Dr. Watanabe$B!G(Bs analysis of perceptual learning makes us hunger for complementary studies of the changes in IT neurons and the pathways toward them that must be responsible for it.
The analysis of cortical networks for the planning of action and the direction and control of movement was the theme of a number of talks. Dr. Tanji clarified the cortical representations at different levels in the motor hierarchy. The connections among areas involved in the planning of action were themes of Dr. Takada. The representation of current and desired location in the primate brain has been of enormous interest, and virtual reality navigation in monkeys with fixed heads, as presented by Dr. Taira, gives us insight into some of the cortical activity involved in this process.
The role of systems neuroscience in the recovery from neural degeneration or injury was a theme of a few presentations. Advances in the physiology of the basal ganglia loop and its disorders were presented by Dr. Nambu. The synthesis of molecular biology and traditional physiological approaches to systems neuroscience was particularly clear in Dr. Isa$B!G(Bs analysis of propriospinal neurons and the cortical mechanisms that can compensate for spinal cord injury.
Issues of representation of plans and concepts, and ultimately language are the most crucial and the most difficult aspects of understanding how the operation of the cerebral cortex makes us reasoning beings. I remember a dinner with David Hubel and David Marr when I was a postdoc: They disagreed about how one should study how the brain manages an American football game. Prof Hubel thought that one should make recordings from cells in the brain of the quarterback. David Marr thought that you should watch the calls of the referees and read the rule book. These disparate views have now, to some extent, coalesced. Drs Tanaka, Kawato, and Sakai, who have made major contributions on simpler problems earlier in their careers, have taken on this difficult task. Dr. Tanaka, with his gift for clarity, showed us what various areas of the frontal cortex of monkeys represented as the monkeys were doing their tasks. Dr. Kawato showed us an amazing humanoid robot, but told us how he and his colleagues, not the computers in the robot, set out the representations to be used. He described to us how issues of representation are central to all of his research problems. Dr. Sakai made the case for studying language as an ultimate form of representation, and the possibility of studying it rigorously in the human brain.
I hope that my attempt to weave this meetings talks together, noting how each relates to the different themes, creates in your, as in my, mind an ephemeral textile that will be useful to you as you do the same thing for yourself, consolidating what you have learned here.
International meetings can be enormously useful, as well as pleasant. This meeting gives us much more than a similar investment of time spent reading one another$B!G(Bs papers. For one, we have the chance to ask and answer questions about points we may have misunderstood, or points for which we don$B!G(Bt find the published evidence convincing. The result of such discussions may be more experiments, a different analysis, or sometimes just a clarification. In addition, we get to hear and understand and discuss plans for future directions, which can improve all our future work. We also learn about new tools that our colleagues have created. Finally, the Poster Sessions in particular give us foreigners the opportunity to meet many brilliant and energetic young Japanese student scientists, and they to meet us, forming a basis for future scientific exchanges and postdoctoral fellowships.
Let us end with an expression of thanks to the National Institute of Basic Biology and to Professor Yamamori for this stimulus to progress in neuroscience, and for this celebration of Community between Japanese and Western science.
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