Neuroscientist Zhenyu Gao found it fascinating when, as a student, he first recorded the electric activity of brain cells and saw how they communicate with each other. Twenty years later, his fascination with how the brain works has only grown. ‘The deeper you get into the field, the more you realize that everything is much more complex than how it is presented in textbooks. Do you know the saying “The more you know, the more you realize you don’t know”? That is very applicable to neuroscience and my career. There are still so many gaps in our knowledge about the brain. That keeps the work as a scientist exciting and makes every new discovery worthwhile.’
Two brain regions
Zhenyu focuses on a specific part of neuroscience. He wants to know how the brain controls movements. Because even for everyday movements that you seemingly make without thinking, our brains have to work hard. Picking up a cup of coffee from the table or stepping onto a curb: a lot of calculations are involved.
There are two brain regions particularly important for performing movements. The first is the motor cortex, a piece of brain cortex on the sides of the head. The motor cortex is responsible for planning and initiating movement. People with damage to the motor cortex, for example due to a stroke, have difficulty starting a movement. The second important part is the cerebellum, or the little brain. This is a small but powerful area at the bottom of the brain. The cerebellum makes up only 20 percent of brain volume but contains 80 percent of all brain cells. The cerebellum is important for fine-tuning movement. People with damage to the cerebellum can move, but not very precisely.
Constantly communicating
But it is not as straightforward as it is presented in the textbooks, Zhenyu and his team discovered. ‘We do know that the motor cortex and the cerebellum are important for movement. They each have their own function. But we have discovered that they do not work in isolation; they are not separate lego blocks. There are all kinds of connections between the cerebellum and the motor cortex: they are constantly communicating with each other.’
The question Zhenyu wants to answer is: how do the motor cortex and the cerebellum work together to plan and execute a movement? ‘We know they are connected, but we do not yet know what information they send back and forth to each other. And how activity in one region affects the other region.’
‘There are still so many gaps in our knowledge about the brain’
In his quest to answer his questions, Zhenyu benefits from the technological advancements that neuroscience has made since he was a student. ‘At that time, we used one electrode to measure the electric activities of a single brain cell in a mouse. These unique electric activities, the action potentials as we call them, is like the language that neurons talk to each other.’ An electrode is a kind of thin needle that can be very precisely inserted into a specific part of the brain. It is so small that it can measure the electrical signals that a single brain cell emits when the mouse performs a task. ‘But the brain contains billions of cells, so the activity of one does not tell you much. Thanks to technological development, nowadays, we now have electrodes that can measure the activity of not one, but thousands of brain cells at the same time. This for the first time allows us to study the activity of large population of brain cells.’
Zhenyu opens a drawer in his desk and takes out such a modern electrode. The needle glistens and is so thin that it is almost invisible to the naked eye. He gives an example of an experiment in which he uses this technology. ‘We can train a mouse to make a certain movement. For example, to pick up a drop of water with its paw and bring it to its mouth. While the mouse performs this task, we measure with the electrodes what happens in the cerebellum and the motor cortex. This way, we try to get an integrated picture of how brain regions work together.’
Zhenyu can even literally visualize the connections between brain parts. ‘We can genetically modify brain cells so that they light up when they become active. Through a window in the mouse’s skull, we can see under the microscope how different brain cells work together on a movement. I consider myself lucky that we have reached a stage where all these techniques are available.’ Step by step and experiment by experiment, Zhenyu hopes to fill the knowledge gaps about how brain parts work together in movement.
Practical use
At the same time, the neuroscientist is already working on translating that fundamental knowledge for practical use. To do so, Zhenyu relies on insights from the laboratory, he explains. ‘One of the fascinating things is that many of the basic mechanisms the brain uses to control movement are remarkably similar across all mammals, including humans. By studying how the brain controls movement in animal models, we can gain insights into how human brain circuits communicate, adapt, and sometimes malfunction in neurological diseases. The cutting-edge technologies in brain recording and imaging, many of which are being developed right now, hold promise not just for research, but for transforming clinical care as well in the future.’
‘We are developing a way to take measurements of brain activities during surgeries’
Zhenyu himself is already personally involved in translational research. Besides his appointment at the neuroscience department, he has a second appointment with the neurosurgery department of Erasmus MC. ‘Together, we are developing a way to take measurements of brain activities during surgeries, for example, before surgeons remove a brain tumor. The surgeons want to know which part of the brain is diseased and which part is healthy. But to know if you can cut something out, you need to know its function. Now they do this by stimulating different parts of the brain and seeing how the body reacts. But it may be that we miss something with that. We want to make an electrode similar to the one we use for mice. Patients are often awake during this brain surgery, so the idea is that we ask them to make a movement and simultaneously measure which brain parts are involved.’
More knowledge about the brain would also be beneficial for people with paralysis or other movement disorders. Worldwide, work is being done on so-called brain-computer interfaces. This is a technology in which brain signals are measured, digitized, and converted into an action by a computer. For someone with paralysis, such a brain-computer interface could help them move again. Simply put: an implant in the brain captures the electrical signals when someone thinks about a movement. That signal is read and converted into an impulse that is sent to the muscles.
Zhenyu follows the developments with interest. ‘It is a matter of technology: how can you measure, interpret, transmit, and convert the signals into the correct commands for the body? And how do you get that working safely in the patient? That is a technological marvel. If we better understand the function of specific brain regions in controlling movement, it can be very useful for the next generation of brain-machine interfaces. There are already some successful examples; it is not very futuristic. I think we are getting closer to the point where we can make someone with paralysis move again.’
Biomedical research
Through biomedical research, we work to understand basic biological and medical principles. This research is at the heart of medical progress and lays the foundation for innovations that improve care. As stated in Strategy28, Erasmus MC’s strategic plan.
