Humans may be born with preconfigured brains that help us understand the world

In a fascinating new study, scientists used pieces of human brain tissue to demonstrate that neural circuits produce electrical patterns very early in the development process, even before senses are active.

These experiments at the University of California, Santa Cruz (UCSC) and other labs suggest that the brain comes with built-in timing rules for thoughts.

Researchers tracked signals in organoids – lab grown pieces of human brain tissue – and in slices of newborn mouse cortex that never received sensory input.

Across these preparations, neurons lit up in repeating ordered patterns, hinting that the brain carries an internal script for making sense of the world.

Early brain circuit activity

At the center of this project is Tal Sharf, an assistant professor of biomolecular engineering at UCSC. His research focuses on how the brain’s neural circuits assemble themselves before sensory experience shapes them.

Neuroscientists have known for years that brain activity in adults is not just random noise – it follows structured sequences when animals move, remember, or rest quietly.

Classic work in rodents showed that hippocampal cells can “preplay” paths an animal will walk, suggesting activity patterns exist before experiences arrive.

Those repeating chains are called neuronal firing sequences (NFS), which are ordered bursts of nerve cell spikes over very short periods of time.

They are thought to be units the brain uses to send information from one place to another and to stitch events in time.

Scientists have argued over whether these sequences appear only after months of sensory input.

Sharf and his collaborators set out to test if any are present before a brain has had the chance to sense the outside world.

Growing mini brains

To tackle that question, the group turned to organoids that can mimic parts of the human cortex.

One review described how these brain cultures capture early developmental stages and are used to study autism and Alzheimer disease.

Earlier experiments from Sharf and colleagues showed that brain organoids form circuits where neurons connect, synchronize, and react to drugs that shift activity.

Those findings suggested that these models are not just static tissue samples but active networks that can learn and change.

Another study found that cortical organoids gradually develop complex oscillatory waves that resemble patterns seen in preterm infant brain recordings.

Together with the new work, these results strengthen the idea that organoid networks follow internally guided programs as they mature.

In experiments, the team grew organoids from human stem cells and placed slices of tissue onto microelectrode arrays, which are flat chips with many recording sites.

Those arrays let the researchers separate signals from hundreds of neurons at once and follow how each cell fired over minutes of spontaneous activity.

Early brain circuit sequences

When they looked at these recordings, the scientists saw that bursts of activity swept through organoids in ordered steps, rather than as random flashes.

Each burst followed a specific schedule, with some neurons firing early and others firing late, forming sequences that match a built in wiring plan.

Within those patterns, the analysis revealed a fraction of cells that fired on every burst in a fixed order, creating backbone for the sequence.

Many other cells participated sometimes or at varying times, adding flexibility around that backbone so the network could explore combinations without losing its rhythm.

The timing of these sequences resembled patterns measured in adult cortex, where spontaneous events outline the range of sensory responses a circuit can produce.

“These cells are clearly interacting with each other and forming circuits that self-assemble before we can experience anything from the outside world,” said Sharf.

That isolation from outside input means the ordered firing reflects sequence rules encoded in the brain circuit network itself not carved by experience.

This idea fits with a view in developmental neuroscience that some circuits start with scaffolds which later get tuned by senses and by learning.

From lab to newborn mice

To see if patterns arise in brain tissue, the researchers recorded from slices of the somatosensory cortex in mice, which is tissue that processes touch signals.

These mice were at an age when most senses besides smell are still developing, so their cortices had received only limited outside input.

In those slices, neurons fired in recurring bursts that unfolded in the same order, with a backbone of cells leading the wave and others joining.

That parallel between organoids and living tissue strengthens the case that the underlying sequence rules are built into the way these circuits grow.

In flat cultures of cortical neurons, the cells produced bursts of activity but lacked the ordered sequences that appeared in organoids and slices.

That contrast suggests that having a three-dimensional layout with diverse cell types is important for letting backbone sequences form and persist.

Similar timing motifs in lab grown human tissue and early mouse cortex argue that sequence-based organization is a general feature of mammalian brains.

It supports the idea that evolution has shaped the brain’s neural circuits so they can assemble maps of time, even before an individual encounters the world.

Implications of preconfigured brains

Because these mini-brains develop from patient or healthy stem cells, researchers can compare how sequences unfold in organoids from people with different conditions.

If a disorder changes when backbone cells fire, or how cells join a sequence, those changes could expose assembly problems before symptoms appear.

Organoid-based models let scientists probe disorders, including microcephaly and epilepsy, giving access to stages of brain growth that cannot be studied directly.

Adding precise measurements of early-firing sequences to that toolkit could help explain why some conditions disturb perception, movement, or cognition from the start.

These recording platforms can track how sequences change after a drug or gene edit, letting researchers search for treatments that restore normal timing patterns.

That approach could be especially valuable for disorders where current medicines blunt symptoms, but don’t correct the underlying wiring problems.

Taken together, the organoid recordings, neonatal mouse slices, and flat culture comparisons point to a brain that starts life with preconfigured firing rules.

Understanding those rules could clarify how infants rapidly learn, and could open paths to treating disorders while the brain is still assembling.

The study is published in Nature Neuroscience.

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