How diversity is driving insights into the brain

Scientists in Japan say that diverse teams and approaches are helping to uncover the brain’s complexity, from memories hiding in the spinal cord to the processing of optical illusions.

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A researcher at RIKEN Center for Brain Science has recently identified a type of neuron in the spinal cord, known as a Renshaw cell (pictured), that recalls learned motor responses independant of the brain neurons initially used to learn the behaviour.Credit: RIKEN CBS

The brain is one of the most sophisticated systems known, embodying remarkable complexity — and diversity. Structurally, it houses roughly 86 billion neurons interconnected by trillions of synapses, forming the elaborate networks that underpin complex cognitive functions. 

Functionally, the brain manages a vast array of processes, from sensory perception and motor control to reasoning and memory, all emerging from layered interactions.

Understanding the brain requires a hugely varied scientific approach, explains Shigeo Okabe, director-elect of RIKEN Center for Brain Science (CBS) near Tokyo, a part of Japan’s national research institute, RIKEN. 

CBS’s researchers work across disciplines and methodologies — from molecular biology and computational modelling to behavioural research and human brain imaging. CBS also hires and fosters junior faculty from widely varied backgrounds, which Okabe says is paying off in groundbreaking scientific discoveries.

In fact, several researchers have recently made striking breakthroughs that are reshaping our understanding of the central nervous system’s role in an organism’s behaviour.

Louis Kang (far left) heads the Neural Circuits and Computations Unit.Credit: RIKEN CBS

Beyond the brain 

In 2024, CBS researcher, Aya Takeoka, and her team reported an unusual type of memory based in the nervous system outside the brain1. The study, which was published in Science, used mice to pinpoint the involvement of two distinct classes of neurons — which transmit signals in the body and brain — in a phenomenon known as ‘spinal motor memory’. Importantly, one of these classes of neurons can retain memories in the spine, without the brain.

“It was exciting to find that the neurons responsible for learning in the spinal cord — the dorsal horn neurons — were not important once ventral spinal cord neurons had ‘learned’ information,” says Takeoka. These ventral spinal cord neurons, known as Renshaw cells, were found to be critical for recalling the appropriate response to the same stimulus without the brain.

“In summary, the spinal cord establishes the ‘rules’ of how to adapt through dorsal horn cells, but once that learned relationship is established, Renshaw cells retain the memory,” she says. “Understanding the functional role of these distinct spinal cord neurons could help scientists to develop better rehabilitation strategies for motor disorders,” she adds.

In her study of mice, Takeoka used a technique known as optogenetics — a means of controlling cells with laser light — to identify the cells and neurons responsible for each phase of learning.

Crucially, despite spinal motor memory occurring quickly, Takeoka and her team were able to clearly capture it in action by measuring nerve activity within the spinal cord.

“We are proud to say that we are among the first to do so,” Takeoka says. “It’s fascinating to see how the spinal cord, often seen as a simple relay station, actually plays a critical role in complex motor learning processes.”

Fumi Kubo is doing cutting-edge work on motion-processing.Credit: RIKEN CBS

Fish perception 

CBS neuroscientist, Fumi Kubo, uses a different model animal to study how visual system inputs are processed in the brain.

As detailed in a 2020 paper published in the journal Neuron, Kubo and her collaborators used an optical illusion known as the ‘motion aftereffect’ to isolate the small number of neurons in larval zebrafish necessary for motion processing.

The motion aftereffect is a sensation felt after the visual system has adapted to looking at something that is continuously moving. It then makes it seem as if stationary objects are moving in the opposite direction.

By exploiting the motion aftereffect in zebrafish, Kubo and her team applied optogenetics and calcium imaging to pinpoint the specific neurons involved. Her lab’s analysis found that of approximately 500 neurons that respond to motion, only a small subset are necessary for motion processing. “We found that roughly 10% of these neurons are critical for this process,” she says.

Kubo and her lab now hope to identify how these fit in with the entire motion processing brain circuit. But she says that this will call for the use of additional methods such as molecular profiling and morphological reconstruction, which Kubo and her lab have pioneered.

These kinds of insights, she says, have been accelerated by the diversity at CBS. “Many of the RIKEN trainees are from outside Japan,” says Kubo. Her lab, for example, has had graduate students from places as far flung as Taiwan and Kazakhstan. “Having a diverse team allows us to approach problems from multiple angles,” she says. “It leads to more creative solutions and a richer understanding of the complex systems we study.”

RIKEN Center for Brain Science

While neuroscience has made remarkable strides in recent years, each technical advancement sheds light on the brain in a fragmented way, says Shigeo Okabe, director-elect of RIKEN Center for Brain Science (CBS). Given the highly networked organization of the brain itself, a concerted, multi-dimensional and cross-disciplinary effort is needed to gain insight.

To this end, CBS brings world-leading experts together in a collaborative environment, connecting them to the wider community of international partners, as well as government and industry networks.

Research at CBS is focused on three key areas. Firstly, CBS studies neural circuit function across a spectrum of species, from invertebrates to humans. Secondly, CBS bridges the gap between basic and clinical neuroscience with novel animal models of diseases and a focus on circuit dysfunctions. Thirdly, CBS researchers are building new computational neural network models and artificial intelligence to understand and improve both human behaviour and communication.

The variety of research topics — from theoretical neuroscience to human functional MRI studies — encourages diverse thinking and a cross-pollination of ideas and techniques, says Okabe. This diversity extends to its teams, which includes a large number of female and foreign researchers, and the centre is working to further promote the diversity of its researcher community.

Louis Kang, for example, is a theorist from the United States, building simulations of neural networks to better understand how new memories are formed.

For Kang, who has graduate degrees in both physics and medicine, this could help address diseases such as dementia. The key, he says, is keeping his simulations close to what has been observed in the brain. As a result, he interacts a lot with CBS experimentalists, including their findings in his models and testing his hypotheses with their data.

Kang, who came to CBS after a postdoctoral fellowship at the University of California, Berkeley, says he was attracted to the centre because of its collaborative philosophy and its diverse, high quality work from the molecular level to human neuroimaging. Today, he heads its Neural Circuits and Computations Unit.

Ultimately, says Okabe, CBS’s goal is to enhance mental and psychological well-being in society. He sees early-career researchers from diverse backgrounds, such as Kang’s, as the key to achieving this goal.

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