Japanese scientists just built human brain circuits in the lab

The study was published in the journal Proceedings of the National Academy of Sciences of the United States of America.

Why Cortical Neural Circuits Matter

The cerebral cortex contains many different types of neurons that must communicate effectively with one another and with other brain regions. These connections are essential for core brain functions, including perception, thinking, and cognition.

In people with neurodevelopmental conditions such as autism spectrum disorder (ASD), these cortical circuits often develop or function abnormally. Because of this, understanding how neural circuits form and mature is critical for uncovering the biological roots of these disorders and for developing new treatments.

The Thalamus and Its Role in Brain Wiring

Earlier research in rodents has shown that the thalamus plays an important role in organizing neural circuits in the cortex. However, how the thalamus and cortex interact during circuit formation in the human brain has remained largely unknown.

Studying this process directly in humans is difficult due to ethical and technical limitations on obtaining brain tissue. To overcome these challenges, scientists have turned to organoids, which are three dimensional structures grown from stem cells that resemble real organs.

From Organoids to Assembloids

While organoids are useful, a single organoid cannot capture the complex interactions between different brain regions. To study neural circuit formation more realistically, researchers use assembloids, which are created by physically combining two or more organoids.

Professor Fumitaka Osakada, graduate student Masatoshi Nishimura, and their colleagues at the Graduate School of Pharmaceutical Sciences at Nagoya University developed assembloids that model interactions between the thalamus and the cortex.

The team first generated separate cortical and thalamic organoids from human iPS cells. These organoids were then fused together, allowing the researchers to observe how the two brain regions interact as they develop.

Mini Brain Circuits That Behave Like the Real Thing

The researchers observed that nerve fibers from the thalamus grew toward the cortex, while cortical fibers extended toward the thalamus. These fibers formed synapses with one another, closely resembling the connections seen in the human brain.

To assess how this interaction affected development, the team compared gene expression in the cortical region of the assembloid with that of a standalone cortical organoid. The cortical tissue connected to the thalamus showed signs of greater maturity, indicating that thalamus cortex communication promotes cortical growth and development.

Thalamic Signals Drive Neural Synchrony

The scientists also examined how signals traveled through the assembloid. They found that neural activity spread from the thalamus into the cortex in wave like patterns, creating synchronized activity across cortical networks.

To understand which neurons were involved, the team measured activity in three main types of cortical excitatory neurons: intratelencephalic (IT), pyramidal tract (PT), and corticothalamic (CT).

Synchronized activity was seen in PT and CT neurons, both of which send signals back to the thalamus. IT neurons, which do not project to the thalamus, did not show the same synchronization. This suggests that thalamic input selectively strengthens specific neuron types, helping them form coordinated networks and mature functionally.

A New Tool for Studying Brain Disorders

By successfully recreating human neural circuits using assembloids, the researchers have established a powerful new platform for studying how brain circuits form, function, and differ across cell types.

Osakada explained the broader significance of the work, saying, "We have made significant progress in the constructivist approach to understanding the human brain by reproducing it. We believe these findings will help accelerate the discovery of mechanisms underlying neurological and psychiatric disorders, as well as the development of new therapies."