vol.32 Department of Neurobiology

The Department of Neurobiology is engaged in research on axons in the brain. In the neural circuit of the brain, thin cable-like structures called axons transmit electrical signals at high speed. However, since the axons of the brain are extremely thin, it has been difficult to directly capture their electrical activity. In recent years, the method of making brain slices has made great strides, and it has become possible to prepare high-quality slice specimens that enable direct recording from an axon (subcellular recording).

“Advances in the brain slice method have made it possible to directly record axon activity, which has been difficult in the past. In this department, we are conducting research toward understanding the operating principle of neurons using subcellular recording from the terminals of a single axon,” Professor Haruyuki Kamiya says. In 2018, Professor Kamiya’s research group succeeded in measuring nerve signals from a single nerve axon in a mouse hippocampus. It was discovered that action potentials (digital signals in the brain) are modulated into analogue in response to neural activity. A commonly accepted theory had been that digital signals in the brain follow the all-or-none law, but Professor Kamiya’s research group found that analogue modulation occurs there. When doctor course student Mr. Shunsuke Ohura who was in the group at that time, was conducting an experiment in which brain slice specimens were prepared from a mouse hippocampus and electrical stimulation was applied to nerve axons called mossy fibers, he discovered that repeated stimulation at short intervals slightly diminished the size of the action potentials of nerve axons. As a result, it led to the finding of analogue fine-tuning from 1 to 0.9 (Figure 1) although the size of action potentials had been considered invariant (1).

In the department, they are conducting research that incorporates computer simulation as well as experiments. Subcellular recording from a single axon, which is very difficult, and elucidation of principles and mechanisms using computer simulation – both are conducted in a single laboratory. Professor Kamiya says that he wants to convey to students the fun of the “two swords.”

“Electrophysiology is an orthodox experimental method with a long history. In recent years, however, it has become possible to capture the phenomenon in milliseconds due to the development of the patch-clamp and other techniques. The number of researchers who are tackling subcellular recording is still small, and it is an area where new discoveries are likely to be made. By modeling the hypothesis derived from such a discovery and reproducing it on a computer, a more reliable conclusion can be drawn. Some of such research results will have a great impact, overturning or rewriting the previous commonly accepted theories and concepts,” the professor says.