Laboratories

Laboratory of Informatics of Biological Functions(IMCB) Doesn't recruit students for the academic year 2018

Associate Professor Kei ITOH
Institute of Molecular and Cellular Biosciences(HONGO)
E-mail: itokei{at}iam.u-tokyo.ac.jp
Lab HP

Introduction

 We still understand little about how the brain works as an information-processing device,and how its circuits are created. The brains of high-order vertebrates are so large and complex as to defy overall comprehension, so our lab uses Drosophila as a model organism for systematically studying the structure,function,and developmental processes of neuronal circuits. Drosophila brains have a relatively simple structure,yet still perform advanced information processing that allows for rich genomic information and research involving the application of a variety of genetic engineering techniques.

1. Analysis of brain structure

 We have created an image database of brain developmenta patterns from larvae and adult Drosophila using a collection of over 4500 strains of GAL4 enhancer trap specimens, covering one-seventh of the full locus. Screening these data for trains that characteristically label various neural circuits and analyzing the structural details allows determination of circuits by following in turn the sensory information flows for vision,smell,and hearing from sensory nerves to higher order centers (see igure). We also perform detailed analysis of information flows related to the inputs and outputs of peripheral brain regions responsible for learning and other advanced functions.

Fig ure: Three-dimensional structures showing the variety of pathways for visual information from the compound eyes to the brain,labeled using GAL 4enhancer traps

2. Brain function analysis

 By combining in situ hybridization using the gene database from the genome project and various combinations of antibodies, we can map how the nerves discovered in (1) release and accept neurotransmitters. By forcibly expressing specific genes that transfer or inhibit neural function and investigating the resulting influence on behavior such as light orientation and mating, we can analyze correlations with division of functionality in neural circuitry.

3. Analysis of brain development

 By analyzing over time the formation process of the identified neural circuits under normal circumstances and after forcible expression or mutation of various genes, we are able to study the process of proper nerve fiber extension, circuit formation, and dynamic reconfiguration in response to changes in the microenvironment. Through the development of a new cellular labeling method we were able to visualize the formation of all neural circuits formed by the descendants of a single neural stem cell in an adult brain,and thereby discover that many neural network modules are dependent on cell lineage. Viewing the complex neural circuitry as an assembly of module constructs allows us to analyze the mechanisms behind neural circuit formation, focusing on the interaction between neurons and glial cells.

4. Brain bioinformatics

 Computer simulations are still limited to modeling extremely simplified “neural networks,”and we are far from simulating brain functions based on actual neural circuits. In science fiction, there are often depictions of computers with features similar to the human brain, but the reality is that we are still unable to duplicate the structure of even relatively simple brains,like that in Drosophila. Therefore, we leave the duplication of fly brains in silicon as a longterm goal, and for the present, focus on extracting topological information related to the three-dimensional structures of the circuits found therein, and investigating ways of compiling this information into databases.

Laboratories

The University of Tokyo
Graduate School of Frontier Sciences, The University of Tokyo

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