To begin, could you introduce the Shigeru Tanaka Lab and the various themes studied?

The objective of my lab is to understand how the brain works – a goal shared with most other neuroscience laboratories in the world. A key feature of the lab is the synergy we create between theoretical and experimental studies. We do not stick to a particular theoretical method, but work in a flexible, versatile way, engaging in experimental research on human and animal brains where necessary and collaborating with theoretical and experimental researchers across various fields in neuroscience. We use the theory of activity-dependent self-organisation to reproduce functional columns in the sensory cortex; topology theory to explain the emergence of singularities in the orientation-direction joint map in the cat visual cortex; and mathematical analysis of functional magnetic resonance imaging (fMRI) signals to reconstruct the three-dimensional structure of orientation columns. Most recently, we have started to investigate higher brain functions, such as working memory and the brain’s representation of subjective impression.

Can you offer an overview of your working memory model of neural networks in the prefrontal cortex, basal ganglia and thalamus?

Many researchers have reported on the importance of the prefrontal cortex in the performance of working memory, visualising activity patterns associated with various tasks using fMRI. The function of the basal ganglia is particularly emphasised in the context of reinforcement learning associated with dopamine release from the terminals of mesencephalic dopaminergic neurons. Our mathematical model of a working memory network is composed of prefrontal cortex-basal ganglia-thalamus loops to reproduce human performance of the 1-2-AX task.

In the model, we took into account bistable resting membrane potential experimentally observed at medium spiny neurons in the striatum and incorporated direct and indirect pathways. The direct pathway loops in the model reproduce sustained neuronal activity for the maintenance of information, and the indirect pathway loops shut down activity in the direct pathway for discarding the maintained information, which are triggered by external stimuli. The model successfully showed correct responses to all orders of symbols presented.

In what ways does your cerebellar circuit model challenge the established view of the cerebellum’s information-processing capability?

A well-known cerebellum model is a perceptron model proposed by David Marr, James Albus and Masao Ito. It is also known that a simple perceptron is limited in its computational power. By contrast, our cerebellum model – a kind of so-called liquid state machine – is free of this limitation, and capable of performing any logical operation. In addition, the model can represent the passage of time, which is regarded as one of the important cerebellar functions. When we rebuilt a realistic model taking into account

individual types of neurons in the cerebellum, we were able to successfully reproduce an eyelid conditioning experiment on rabbits.

Are you collaborating with any other organisations or individuals? How important is collaboration to your research?

In my ongoing research on the visual cortex, I am working with Dr Takamasa Yoshida from the RIKEN Brain Science Institute on the topic of two-photon calcium imaging of neuronal microcircuits in the mouse visual cortex; Professor Yoshio Hata of the Medical School of Tottori University, conducting anatomical studies of afferent inputs from the visual thalamus to visual cortex in mice; Dr Toru Takahata from Vanderbilt University, Tennessee, USA, to reveal functional architecture in the primary visual cortex of New World monkeys using immediate-early gene expression; and Professor Masanobu Miyashita from Numazu National College of Technology, mathematically modelling the activity-dependent self-organisation of functional architecture in the visual cortex and visual image decoding from the ensemble of neurons in the model visual cortex.

My collaborators in human brain research are Professor Maki Sakamoto at University of Electro-Communications and Dr Tomoki Fukai from the RIKEN Brain Science Institute, Japan, working on fMRI measurement of brain representation of subjective impression evoked by Japanese onomatopoeia. The objective of this study is to elucidate the generation mechanisms of qualia.

Do you intend to showcase your work at any forthcoming events?

We attend the Society for Neuroscience Meeting held in the US every year to give presentations of our work, and we will showcase some of our research achievements at this year’s meeting – Neuroscience 2014 in Washington, DC, on 15-19 November.

Professor Shigeru Tanaka is researching the formation and plasticity of information representation within the visual cortex of young animals, as well as higher brain functions such as working memory

Activity-dependent self-organisation

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PROFESSO

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OVER 40 YEARS ago, researchers Colin Blakemore and Grahame F Cooper from the University of Cambridge, UK, pioneered experiments which placed kittens in a striped environment for several hours a day for several months, then recorded their neuronal responses to various visual orientations. Results reported in Nature in 1970 revealed a strongly biased distribution of neurons responsive towards the visual orientation experienced by the kittens. However, a later, similar experiment reported no significant bias in neuronal distribution.

Located at the back of the mammalian brain, the visual cortex is responsible for processing visual information. While it is generally accepted that functional maps comprising columns of neurons within the cortex are formed based on neural activity, there remains disagreement over the

extent to which visual experience contributes to the formation of these maps during brain development. The majority of neurons in the mammalian primary visual cortex respond to contours within visual images, with individual neurons having stronger responses to particular orientations. A better understanding of how neurons create functional maps and develop their responses has implications for our ability to treat various forms of cortical dysfunction.

EXPERIENCE-DEPENDENT PLASTICITY

A simple interpretation of the function of the primary visual cortex is that it detects contours of visual images as a first analysis step in the generation of visual percepts in higher visual centres, but some researchers – such as Professor Shigeru Tanaka from the University of

Electro-Communications in Tokyo, Japan – do not subscribe to this.

Tanaka’s lab is investigating the development of the mammalian visual cortex and how its neurons selectively respond to contour orientations of visual images. “In some species such as cats and ferrets, neurons cluster to form columns penetrating the grey matter, arranged along the cortex such that the preferred orientation is almost continuously represented throughout the cortex,” outlines Tanaka. “We call this representation the ‘orientation map’.” In the rodent visual cortex, neurons also selectively respond to the orientation of contours but, in contrast, there is no orderly orientation map, with preferred orientation represented in a more haphazard fashion.

There are still, however, debates surrounding experience-dependent plasticity of orientation selectivity. Tanaka’s research aims to settle this controversial issue, with experiments designed to continuously expose kittens to a single visual orientation. This is achieved through the use of specially fabricated, cylindrical, lens-fitted goggles, which are stably mounted on the kittens’ heads and easily detached for daily cleaning.

The project differs from previous experiments on kittens, which have employed cylindrical isolation rooms whose inner walls are painted with stripe patterns, or rubber masks fitted with cylindrical lenses. These experiments limited the animals’ orientation experience to several hours a day, while they spent the rest of the time with their mothers in a dark room. The use of light goggles enables Tanaka’s animals to experience stripe-like patterns continuously for more hours each day and for a longer period – up to a few months. The animals can also stay with their mothers to be cared for and play with their litter mates – except for their visual experience, they live a natural life.

ORIENTATION SELECTIVITY

Tanaka and colleagues’ hypothesis is that goggle-reared animals are blind in inexperienced orientations – that is, their visual cortices are only capable of decoding stripe patterns which match the orientation in which they are experienced, or under which their visual cortex has developed. To confirm this speculation theoretically, his team conducts simulations using a self-organisation model.

The researchers were able to reproduce the orientation maps observed in goggle-

The researchers were able to reproduce the orientation maps

observed in goggle-reared kittens, demonstrating a clear over-

representation in line with experienced orientation

Mammalian mind mappingResearch into the cerebral cortex at the University of Electro-Communications in Tokyo, Japan, offers hope for new human treatments of cortical dysfunction and to improve quality of life in ageing societies

PROFESSOR SHIGERU TANAKA

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reared kittens, demonstrating a clear over-representation in line with experienced orientation. “We then applied a decoding algorithm to reconstruct visual images from activity patterns in the model cortex,” Tanaka explains. “Surprisingly, any orientated stripe patterns were reconstructed, even though the accuracy of decoded patterns depended on the orientation of the stripes: sharp stripes were decoded at the exposed orientation, whereas noisy stripes were decoded at unexposed orientations.”

The Tokyo team uses intrinsic signal optical imaging to examine how orientation selectivity changes within neuronal populations in cats. For their mouse experiments, they employ two-photon calcium imaging. While intrinsic signal optical imaging works well for reconstructing orientation maps, it does not reveal the activities of individual neurons. This makes it less well-suited to experiments on mice, as their random distribution suggests that the preferred orientations of their individual neurons may be averaged out over the population. Two-photon calcium imaging is better-suited to mice as, unlike intrinsic signal optical imaging, it permits simultaneous measurement of the activities of individual neurons.

CAT AND MOUSE

The results of these studies suggest that the orientation selectivity of individual neurons is not crucial for visual information processing, and that the variety of neuronal response properties may play a more important role in the preservation of visual signals conveyed from the retinas, even under the effects of a noisy neural environment in the cortex. The data also demonstrate that in young animals, neuronal alignments can change if they experience a single visual orientation for just one or two weeks, shifting toward that which the animal is experiencing. These changes in experience-dependent orientation representation are predicted by Tanaka’s self-organisation model.

There are wide implications of this finding. For instance, the goggle rearing method can produce model animals which exhibit meridional amblyopia – a type of cortical dysfunction induced by astigmatism which is also found in human children. These animal models might therefore have applications for human healthcare in helping to tackle the condition early.

MORE QUESTIONS

“We still have unanswered questions about orientation plasticity,” admits Tanaka. “Only one week after goggle rearing, the reorientated neurons occupy a large cortical territory. If kittens are reared with goggles continuously for one to two months, we would have expected

them to occupy the whole of the visual cortex.” Somewhat counterintuitively, this has not proven to be the case. Prolonged goggle rearing produces a moderate over-representation of the experienced orientation which remains robust and unchanged afterwards, leading Tanaka to hypothesise that there may exist as-yet-unknown homeostatic mechanisms which restore orientation maps to some degree.

Mathematical modelling will play a vital role in answering remaining and new questions related to this work. Tanaka plans to use two-photon imaging to elucidate microcircuits in the cerebral cortex of animals, while leveraging functional magnetic resonance imaging to visualise macro-scale activity patterns in the human brain.

QUALITY OF LIFE

Along a different line of research, Tanaka is one of the core members of a newly established research facility – the Brain Science Inspired Life Support Research Center – which is conducting innovative research on life support technologies for the elderly. Advances in this area are particularly urgent in countries with aged societies – in Japan, the most aged country in the world, over 21 per cent of people are 65 or over. The new Center’s mission focuses on advancing technology to enhance quality of life for the elderly, and it is Tanaka’s hope that the lab will grow, not only to help in adding to understanding of how the brain works, but also to provide engineers with the basic knowledge essential to driving technological healthcare innovation.

THE SHIGERU TANAKA LAB

OBJECTIVES

• To describe mathematical models of the cerebellum, basal ganglia, prefrontal cortex and sensory cortices based on experimental observations to understand how the brain works as a whole

• To elucidate the mechanisms of visual information representation and critical-period plasticity in the mammalian primary visual cortex

KEY COLLABORATORS

Dr Takamasa Yoshida; Dr Kazunori O’Hashi; Dr Sochiro Nagao; Dr Tomoki Fukai, RIKEN Brain Science Institute, Japan • Professor Masanobu Miyashita, Numazu National College of Technology, Japan • Professor Yoshio Hata, Tottori University Medical School, Japan • Dr Toru Takahata, Vanderbilt University, Tennessee, USA • Professor Chantal Milleret; Dr Jérôme Ribot, Collège de France, France • Principal Research Scientist Chi-Sang Poon, Massachusetts Institute of Technology, Massachusetts, USA • Professor Seong-Gi Kim; Professor Mitsuhiro Fukuda, University of Pittsburgh, Pennsylvania, USA • Dr Nicolangelo Iannella, University of Adelaide, Australia • Dr Tadashi Yamazaki; Professor Testuro Nishino; Professor Maki Sakamoto, University of Electro- Communications, Japan

FUNDING

Grant-in-aid for scientific research: grant # 24500324, 21500268, 23300055

Research grant of the Artificial Intelligence Research Promotion Foundation

CONTACT

Professor Shigeru Tanaka Head, Shigeru Tanaka Lab

University of Electro-Communications 1-5-1 Chofugaoka, Chofu Tokyo 182-8585 Japan

T +81 42 443 5534 E shigeru@uec.ac.jp

http://tanaka-lab.net

PROFESSOR SHIGERU TANAKA graduated from Tokyo University and obtained his PhD in Physics in 1986. He became a laboratory head in the RIKEN Frontier Research Program in 1994 and Head of the Laboratory for Visual Neurocomputing in the RIKEN Brain Science Institute in 1997. In 2013, he accepted the role of Professor within the Brain Science Inspired Life Support Research Center at the University of Electro-Communications.

Orientation maps reconstructed from optical imaging in the visual cortices of both hemispheres in normally reared (A) and goggle-reared (B) kittens (exposed to only vertical orientation). Color indicates preferred orientation and brightness indicates selectivity to the orientation. Blue, red, yellow and green correspond to preferred orientations of 0° (horizontal), 45°, 90° (vertical) and 125°, respectively. Left, right, top and bottom of each figure correspond to anterior, posterior, right and left, respectively.

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INTELLIGENCE

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