Researchers at UCLA have used human stem cell-derived brain assembloids to recreate the electrical shifts and synchronized slow brain waves produced by general anesthesia. Published in the British Journal of Anaesthesia, the study demonstrates that a minimal cortical circuit can generate these signature rhythms without input from the thalamus.
UCLA Researchers Use Human Assembloids to Model General Anesthesia
Scientists have long understood the molecular targets of anesthetics and the whole-brain changes that occur during sedation. Yet bridging the gap between molecular binding and large-scale brain activity remained a significant hurdle in neuroscience according to a study published in the British Journal of Anaesthesia. To address this, investigators at the UCLA Broad Stem Cell Research Center turned to simplified human brain models.
When exposed to propofol, the engineered circuits produced the broad, slow electrical oscillations typically recorded on an electroencephalogram during general sedation.
How Propofol Alters Neuronal Firing and Network Synchrony
The transition from wakefulness to unconsciousness under propofol involves a paradoxical shift in cellular and network behavior. While individual neurons quiet down and reduce their firing rates, the overarching electrical rhythms of the tissue grow larger. This occurs because large populations of cells begin firing in strict coordination.
It’s a little counterintuitive. Individual neurons become less active, but the overall brain waves become larger, because many neurons begin changing their activity in synchrony.
To verify that this phenomenon relied on known pharmacological pathways, the laboratory blocked the specific receptors targeted by propofol, which eliminated the slow-wave effect entirely.
Resolving the Debate Over Cortical Circuitry Without the Thalamus
Neuroscientists debated whether slow brain waves during anesthesia required loop circuits involving deep structures like the thalamus or whether the cerebral cortex could drive them independently.
This human model bridges two long-standing extremes in neuroscience. Investigators can now connect molecular receptor binding directly to macroscopic network recordings in a controlled human tissue environment.
Broad Clinical Applications for Traumatic Brain Injury and Coma
Aside from standard anesthesia, the study authors observed that the system could assist in evaluating potential medications and exploring why people react differently to anesthetics, such as cases of unintended awareness while under. For medical professionals working in intensive care and surgical units, grasping these cellular network patterns is essential for overseeing sedation and tracking patient awareness.
We’re excited about these models’ potential not just for studying anesthesia, but as a tool we can use more broadly to understand how brain networks become disrupted in other disorders that profoundly alter brain dynamics like traumatic brain injury.