Research Strategy Department Introduction of leading researchers at HU

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Interview of  Professor Kouichi HASHIMOTO

Analysis of the Cerebellar Mechanisms for Timing Control

Program AMED Advanced Research & Development Programs for Medical Innovation (PRIME)
Researchers selected in the FY 2022

Real Time Measurement and Control of Neuronal Electrical Activity

My research focuses on electrophysiology, where I study the electrical signals of neurons by recording their activity at both single-cell and network levels using microelectrodes. Through these recordings, I have investigated synaptic function, neuronal network dynamics, and their influence on animal behavior.

My interest in the brain began during my undergraduate years when I read a book written by Professor Nakaakira Tsukahara, which deepened my interest in neuroscience.

We use glass or metal microelectrodes to record and stimulate neurons. We have recently also used optogenetics to manipulate neuronal activity in the brain. While electrical stimulation using electrodes unselectively activates neurons around the tip of the electrode, optogenetics allows us to selectively control specific neuronal populations by using light-sensitive ion channels or transporters.

One of the most captivating aspects of electrophysiology is its ability to capture neuronal activity in real time. Neural signals fluctuate within milliseconds (1/1000th of a second), and the ability to directly observe these rapid changes provides invaluable insight into how the brain processes information.

How Do We Control Timing in Our Brains?

My research project, “Analysis for the cerebellum-dependent timing control,” was selected for the Advanced Research & Development Programs for Medical Innovation of the Japan Agency for Medical Research and Development (AMED) in 2022. This project aims to reveal the cerebellar circuits that regulate timing perception in animals.

Timing control and perception have been reported to rely on several brain regions including the cerebral cortex, basal ganglia and cerebellum. While the cerebellum is thought to play a key role in sub-second timing, its precise mechanisms remain poorly understood.

The mouse cerebellum and its basic neural circuit

 

To address this, we developed a timing task for mice using an operant conditioning system.

The subregions of networks crucial for the timing perception are examined using optogenetics. Light-activated Ion channels are expressed in subnuclei of the cerebellar networks. By expressing light-sensitive ion channels in specific cerebellar subnuclei, we can precisely manipulate neuronal activity. If optogenetic stimulation alters task performance, it provides direct evidence that the targeted subregion plays a crucial role in timing control.

From Experimental Observations to New Research Directions

I have previously studied molecular mechanisms for postnatal development of neuronal circuits. In the immature brain, neuronal networks are highly redundant, but through experience and activity-dependent refinement, they become functional.

While advancing research goals is essential, I also believe in the importance of embracing unexpected findings that emerge in experiments. Small anomalies often hold the key to new discoveries, and I am trying to develop these into novel research directions.

In future studies, I would like to actively take on the challenge of utilizing information science and other new methods in my research.