Developing More Natural In-Vitro Neurons for Studying Learning and Memory

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The phrase "neurons that fire together, wire together" explains the principle of neural plasticity observed in the human brain, but neurons grown in a dish typically don’t behave in the same way. Instead, in-vitro neurons form random networks that fire together, which doesn’t accurately reflect how a real brain learns. As a result, the insights gained from studying these networks are limited. However, what if it was possible to create in-vitro neurons that more closely mimic natural brain activity?

Researchers at Tohoku University have successfully used microfluidic devices to reconstitute biological neuronal networks that resemble the connectivity found in animal nervous systems. Their work shows that these networks exhibit complex activity patterns, which can be "reconfigured" through repetitive stimulation. This breakthrough opens up new possibilities for studying the processes of learning and memory.

Published in Advanced Materials Technologies on November 23, 2024, the study highlights how information in certain areas of the brain is encoded in "neuronal ensembles" — groups of neurons that fire together. These ensembles change in response to environmental input, which is thought to be the foundation of learning and memory. However, studying this process in animal models is challenging due to the complexity of the brain’s structure.

As Hideaki Yamamoto from Tohoku University explains, the need to grow neurons in the lab arises from the simplicity of these systems, which allow scientists to study learning and memory in a controlled environment. There is a growing demand for these lab-grown neurons to better mimic real brain activity.

To address this challenge, the researchers developed a special model using a microfluidic device — a small chip with tiny 3D structures. This device enabled neurons to connect and form networks similar to those in an animal's nervous system. By adjusting the size and shape of the microchannels that link the neurons, the researchers were able to control how strongly the neurons interacted.

The team discovered that networks with smaller microchannels could maintain diverse neuronal ensembles. For instance, neurons grown in traditional devices typically formed just one ensemble, while those grown with smaller microchannels could form up to six. Additionally, the team found that repetitive stimulation could alter these ensembles, demonstrating a process that resembles neural plasticity, as the cells were reconfigured in response to the stimulation.

This microfluidic technology combined with in-vitro neurons could eventually lead to the development of advanced models that more accurately mimic specific brain functions, such as the formation and recall of memories.