Our brains come pre-wired, say researchers at the University of California at Santa Cruz , whose new work on small brain models shows that electrical activity begins in the brain without any external experiences.
Scientists have long debated the effects of nature versus nurture and wondered how those factors shape even the earliest moments of brain activity. To discover where the earliest electrical impulses originate, the team produced a model of the brain called an organoid, constructed from actual human brain tissue, as reported in a new paper in Nature Neuroscience.
Earliest Electrical Activity
The researchers found that electrical activity in their organoid model, completely removed from any sensory experiences, was not mere random firings, but occurred in structured patterns. This suggests that our brains are preset to process our surroundings in a certain way from birth.
“These cells are clearly interacting with each other and forming circuits that self-assemble before we can experience anything from the outside world,” said senior author Tal Sharf, assistant professor of biomolecular engineering at the Baskin School of Engineering. “There’s an operating system that exists, that emerges in a primordial state.”
“In my laboratory, we grow brain organoids to peer into this primordial version of the brain’s operating system and study how the brain builds itself before it’s shaped by sensory experience,” Sharf said.
Understanding the earliest stages of brain development is an essential scientific goal for advancing the treatment of later-onset issues. This baseline provides researchers with a clear basis for comparison as they investigate how toxins, including microplastics and pesticides, can affect brain development. It will also allow them to better understand where other types of neurodevelopmental disorders begin to deviate from normal functioning.
Modeling the Human Brain
The human brain is often equated with a computer, since both run on electrical signals, which in humans involves the firing of neurons. However, the early human brain is much more challenging to study in depth, as its first cradle in the womb is difficult for observers to penetrate safely. For this reason, organoids, constructed from human brain tissue grown from stem cells, are the easiest way for researchers to watch this organic computer when it boots up for the first time.
UC Santa Cruz hosts the Braingeneers group, a team comprising researchers from UC Santa Cruz, UC San Francisco, and UC Santa Barbara, who are developing new methods for growing and measuring these models to better understand brain development and disorders. Microchips measure the electrical activity of the organoids for the researchers as they perform various tests.
One of the most interesting aspects of organoid research is that it allows scientists to fully isolate brain development from sensory input, in a way that would be infeasible in human subjects. Additionally, the work enables new types of ethical brain research to be conducted with an unlimited number of subjects.
“An organoid system that’s intrinsically decoupled from any sensory input or communication with organs gives you a window into what’s happening with this self-assembly process,” Sharf said. “That self-assembly process is really hard to do with traditional 2D cell culture—you can’t get the cell diversity and the architecture. The cells need to be in intimate contact with each other.”
“We’re trying to control the initial conditions,” Sharf adds, “so we can let biology do its wonderful thing.”
Senses Activate
From the moment the stem cells began assembling themselves into brain tissue, the team was observing their electrical activity. One of the most interesting discoveries was that, just months into normal brain development, the cells were producing electrical signals involved in translating external senses. This would be well before a child experiences any external sensory stimulation and in cells completely cut off from the apparatus that would do so, suggesting that the brain comes prewired to experience and navigate our surroundings.
“These intrinsically self-organized systems could serve as a basis for constructing a representation of the world around us,” Sharf said. “The fact that we can see them in these early stages suggests that evolution has figured out a way that the central nervous system can construct a map that would allow us to navigate and interact with the world.”
Decades of neuroscience research have revealed that the brain does come with default settings, which refine over time with more sensory input. Yet this is the first time that researchers have discovered a baseline for sensory signals produced without any input at all.
“We’re showing that there is a basis for capturing complex dynamics that likely could be signatures of pathological onsets that we could study in human tissue,” Sharf said. “That would allow us to develop therapies, working with clinicians at the preclinical level to potentially develop compounds, drug therapies, and gene editing tools that could be cheaper, more efficient, higher throughput.”
The paper, “Preconfigured Neuronal Firing Sequences in Human Brain Organoids,” appeared in Nature Neuroscience on November 24, 2025.
Ryan Whalen covers science and technology for The Debrief. He holds an MA in History and a Master of Library and Information Science with a certificate in Data Science. He can be contacted at ryan@thedebrief.org, and follow him on Twitter @mdntwvlf.