Replacing skulls with nano-thin films to visualize brain activity: Developing the widest, deepest, and finest optical measurement technique in the world

Q1. What motivated you to become a researcher?

A1. I was captivated by the power of "visualization"

I've always enjoyed coming up with various ideas and been interested in thinking about things from new angles. Through organizing school cultural festivals throughout junior high school, high school, and university, I experienced the fun of turning ideas into reality. That process of deciding what I want to do and then doing has something in common with my work as a researcher today.

One of the things that sparked my interest in the brain was Takeshi Yoro's book Yuinoron. The idea that society is a product of the brain made me realize that understanding the brain is essential to solving problems around the world. I wanted to study the brain while also engaging in "manufacturing" to bring ideas to life, so I chose a course in the Faculty of Engineering where I could study both life sciences and information science.

Later, when I was assigned to a laboratory, I encountered research on imaging living brains using light. I became fascinated by the thrill of making the invisible visible, and that led me to where I am today.

Q2. What research are you currently working on?

A2. Developing the "NIRE method" using light curable resin

I'm working on the development and application of bioimaging techniques to visualize living brain tissue. To understand brain function and neurological diseases, it's necessary to measure not only the activity of individual neurons but also how multiple brain regions coordinate. In conventional approaches, mouse skulls were replaced with flat and hard glass coverslips, but since the brain surface is curved, wide-area replacement was difficult by it.

To overcome this, I developed a technique using polymer thin films (Nanosheet) approximately 100 nanometers thick. Nanosheets are thinner than glass coverslips, have high transparency and flexibility, and they conform closely to the brain surface. By covering the brain with such a nanosheet and reinforcing it with a "light curable resin" that changes from liquid to solid when exposed to ultraviolet light, I succeeded in long-term observation of an ultra-wide area from the cerebral cortex to the cerebellum of a living brain. I named this method the "NIRE method," after the Japanese elm trees (harunire) that are abundant on the campus of Hokkaido University, where I worked at the time.

Currently, I'm applying this method to hibernating hamsters and artificially hibernating mice to elucidate the mechanisms of memory. My future goal is to realize wide and deep optical measurement technology that includes deep brain regions such as the hippocampus, which governs memory.

Q3. A message to those aspiring to become researchers

A3. Find something to be passionate about outside of research

My current research spans multiple fields, including materials engineering, neuroscience, and optics, and it's fascinating how new ideas constantly emerge. On the other hand, it's unrealistic to become an expert in all fields. I feel it's important to value connections with people and collaborate with researchers beyond your own field.

This may sound contradictory, but I encourage aspiring researchers to find something to be passionate about apart from research. It gives you perspectives you can't get from research alone and leads to new discoveries, which ultimately benefit your research.

Personally, I learn the Chinese martial art "Han Shi Yi Quan." This martial art has a teaching called "bu yong li, bu fei nao" (don't use force, don't work the brain), which means the body's natural functions emerge when not consciously using force or being caught up in thought, and this gives me insights for my research. Going forward, I aim to develop technology that "visualizes" living tissue in the widest, deepest, and finest way in the world from a broad perspective.

(Article: Yasuhiro Hatabe)