In-Vitro Neurons Exhibit Advanced Brain-Like Behavior

The phrase “Neurons that fire together, wire together” encapsulates the principle of neural plasticity in the human brain. However, neurons grown in a laboratory dish do not typically adhere to these rules. Instead, cultured neurons often form random, unstructured networks where all cells fire simultaneously, failing to mimic the organized and meaningful connections seen in a real brain. As a result, these in-vitro models provide only limited insights into how learning occurs in living systems, the journal Advanced Materials Technologies reported.

What if, however, we could create in-vitro neurons that more closely replicate natural brain behavior?

A research team at Tohoku University has taken a significant step in this direction. Using microfluidic devices, they engineered biological neuronal networks with connectivity patterns resembling those of animal nervous systems. These networks exhibited complex activity dynamics and demonstrated the ability to be “reconfigured” through repetitive stimulation. This groundbreaking discovery offers a promising new tool for studying learning, memory, and the underlying mechanisms of neural plasticity.

In certain areas of the brain, information is encoded and stored as “neuronal ensembles,” or groups of neurons that fire together. Ensembles change based on input signals from the environment, which is considered to be the neural basis of how we learn and remember things. However, studying these processes using animal models is difficult because of its complex structure.

“The reason there is a need to grow neurons in the lab is because the systems are much simpler,” remarks Hideaki Yamamoto (Tohoku University), “Lab-grown neurons allow scientists to explore how learning and memory work in highly controlled conditions. There is a demand for these neurons to be as close to the real thing as possible.”

The research team created a special model using a microfluidic device–a small chip with tiny 3D structures. This device allowed neurons to connect and form networks similar to those in the animals’ nervous system. By changing the size and shape of the tiny tunnels (called microchannels) that connect the neurons, the team controlled how strongly the neurons interacted.

The researchers demonstrated that networks with smaller microchannels can maintain diverse neuronal ensembles. For example, the in-vitro neurons grown in traditional devices tended to only exhibit a single ensemble, while those grown with the smaller microchannels showed up to six ensembles. Additionally, the team found that repeated stimulation modulates these ensembles, showing a process resembling neural plasticity, as if the cells were being reconfigured.

This microfluid technology in conjunction with in-vitro neurons could be used in the future to develop more advanced models that can mimic specific brain functions, like forming and recalling memories.

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