Researchers in Japan successfully recreated key human brain circuits in the laboratory, revealing the crucial role of the thalamus in cortical development. This breakthrough utilized miniature multi-region brain models called assembloids to observe real-time interactions, offering new avenues for understanding neurological disorders.
The cerebral cortex, essential for perception, thinking, and cognition, relies on intricate neuronal connections. Abnormal development of these circuits is often linked to neurodevelopmental conditions like autism spectrum disorder (ASD). Understanding how these circuits form and mature is vital for uncovering the biological roots of such conditions and developing new treatments.
Previous rodent studies hinted at the thalamus’s importance in organizing neural circuits in the cortex, but direct human evidence remained largely unknown due to ethical and technical constraints. Scientists now leverage stem-cell-derived organoids and assembloids to overcome these challenges, creating models that closely mimic human brain development in a dish.
Unraveling thalamus-cortex interaction
Professor Fumitaka Osakada and his team at Nagoya University developed assembloids by fusing separate cortical and thalamic organoids grown from human iPS cells. Observing these miniature circuits, they noted nerve fibers from the thalamus extending towards the cortex, while cortical fibers extended towards the thalamus, forming synapses akin to those in a developing human brain.
This innovative approach allowed for unprecedented real-time analysis of their interaction. The team compared gene expression in cortical tissue connected to the thalamus with standalone cortical organoids. Results indicated that thalamus-cortex communication significantly promotes cortical growth and maturity, as reported by ScienceDaily on January 7, 2026.
This suggests that the thalamus acts as a hidden conductor, guiding the cortex’s intricate wiring process. The study, published in the Proceedings of the National Academy of Sciences (PNAS), marks a significant step towards understanding human-specific brain development.
Thalamic signals drive neural synchrony
Further investigation into signal transmission within the assembloids revealed 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 specifically observed in PT and CT neurons, both of which send signals back to the thalamus. IT neurons, however, which do not project to the thalamus, did not show the same synchronization. This indicates that thalamic input selectively strengthens specific neuron types, helping them form coordinated networks and mature functionally.
This selective strengthening by thalamic input is crucial for the precise organization of specialized circuits. The findings provide a powerful new tool for studying neurological disorders and could accelerate the discovery of new therapeutic interventions by directly observing human-specific neural processes, moving beyond traditional animal models.
The ability to rebuild human brain circuits in the lab represents a significant leap in neuroscience. This research not only illuminates the thalamus’s critical role in human brain development but also provides an invaluable platform for disease modeling. Future studies using these assembloids could accelerate the discovery of new treatments for conditions like ASD, offering hope for a deeper understanding of the human brain’s complexities.
